Osteoporosis medical therapy: Difference between revisions
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==Overview== | ==Overview== | ||
The | The mainstay of treatment in primary osteoporosis is based on life style modifications. Most of the time in high risk patients and people with past history of osteoporotic [[fracture]], [[Medical therapy template|medical therapy]] is necessary. [[Bisphosphonates]] are the '''''first line''''' treatment for osteoporosis. [[Raloxifene]] is the '''''second line''''' [[treatment]] of osteoporosis in [[postmenopausal]] women, for both treatment and [[prevention]]. [[Denosumab]] is a human [[monoclonal antibody]] designed to inhibit [[RANKL]] ([[RANK]] ligand), a [[protein]] that acts as the primary [[Signal (biology)|signal]] for [[bone]] removal. It is used to treat osteoporosis in older men and [[postmenopausal]] women. [[Teriparatide]] and Abaloparatide are human [[recombinant]] [[parathyroid hormone]]<nowiki/>s used to treat [[postmenopausal]] osteoporosis in women with high risk of [[fracture]] or to increase [[bone]] mass in men with osteoporosis. | ||
==Medical therapy== | ==Medical therapy== | ||
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=== Medical therapy purpose === | === Medical therapy purpose === | ||
* The primary most important goal for treatment of [[osteoporosis]] is to reduce longtime [[fracture]] risk in patients. Increasing [[Bone mineral density|bone mineral density (BMD)]] in response to the treatment is far less important than improvement of clinical aspects of [[osteoporosis]], i.e., [[Osteoporosis|osteoporotic]] [[Bone fracture|fracture]]. Therefore, most of the [[drugs]] | * The primary most important goal for treatment of [[osteoporosis]] is to reduce longtime [[fracture]] risk in patients. Increasing [[Bone mineral density|bone mineral density (BMD)]] in response to the treatment is far less important than improvement of clinical aspects of [[osteoporosis]], i.e., [[Osteoporosis|osteoporotic]] [[Bone fracture|fracture]]. Therefore, most of the [[drugs]] efficacy is measured by the extent it can improve the [[fracture]] risk.<ref name="pmid11893367">{{cite journal |vauthors=Cummings SR, Karpf DB, Harris F, Genant HK, Ensrud K, LaCroix AZ, Black DM |title=Improvement in spine bone density and reduction in risk of vertebral fractures during treatment with antiresorptive drugs |journal=Am. J. Med. |volume=112 |issue=4 |pages=281–9 |year=2002 |pmid=11893367 |doi= |url=}}</ref> | ||
* | * During the treatment, if a single [[fracture]] happens, it may not necessarily reflect treatment failure; and may need to start alternative treatments or patient referral to [[specialist]].<ref name="pmid28761958">{{cite journal |vauthors=Ensrud KE, Crandall CJ |title=Osteoporosis |journal=Ann. Intern. Med. |volume=167 |issue=3 |pages=ITC17–ITC32 |year=2017 |pmid=28761958 |doi=10.7326/AITC201708010 |url=}}</ref> | ||
* [[Calcium]] and [[vitamin D]] supplementation have been found to be effective in reducing the long term [[Bone fracture|fracture]] risk, significantly. In order to suggest the people to use [[vitamin D]] and [[calcium]] [[supplements]], first the [[physician]] has to become sure that patient is not able to obtain the [[nutrients]] through daily intake. The available supplemental ions of [[calcium]] include [[calcium carbonate]] and [[calcium citrate]]; and [[vitamin D3 | * [[Calcium]] and [[vitamin D]] supplementation have been found to be effective in reducing the long term [[Bone fracture|fracture]] risk, significantly. In order to suggest the people to use [[vitamin D]] and [[calcium]] [[supplements]], first the [[physician]] has to become sure that patient is not able to obtain the [[nutrients]] through daily intake. The available supplemental ions of [[calcium]] include [[calcium carbonate]] and [[calcium citrate]]; and [[vitamin D3]].<ref name="pmid24131178">{{cite journal |vauthors=Bauer DC |title=Clinical practice. Calcium supplements and fracture prevention |journal=N. Engl. J. Med. |volume=369 |issue=16 |pages=1537–43 |year=2013 |pmid=24131178 |pmc=4038300 |doi=10.1056/NEJMcp1210380 |url=}}</ref> | ||
=== Medical therapy candidates === | === Medical therapy candidates === | ||
* The | * The National [[osteoporosis]] foundation (NOF) has declared following prescription for [[osteoporosis]] treatment: | ||
** Elder men and [[postmenopausal]] women with past history of [[Osteoporosis|osteoporotic]] [[Bone fracture|fracture]] | ** Elder men and [[postmenopausal]] women with past history of [[Osteoporosis|osteoporotic]] [[Bone fracture|fracture]] | ||
** Elder man and [[postmenopausal]] women with [[Bone mineral density|BMD]]-identified [[osteoporosis]] (T-score ≤ -2.5 [[Standard deviation|SD]]) | ** Elder man and [[postmenopausal]] women with [[Bone mineral density|BMD]]-identified [[osteoporosis]] (T-score ≤ -2.5 [[Standard deviation|SD]]) | ||
** Elder man and [[postmenopausal]] women with -1.0 > T-score > -2.5 SD with high risk of [[Osteoporosis|osteoporotic]] [[Bone fracture|fracture]] | ** Elder man and [[postmenopausal]] women with -1.0 > T-score > -2.5 SD with high risk of [[Osteoporosis|osteoporotic]] [[Bone fracture|fracture]] | ||
** Men with [[hypogonadism]] | ** Men with [[hypogonadism]] in whom [[testosterone]] therapy is contraindicated<ref name="pmid28761958" /> | ||
* The | * The International [[osteoporosis]] foundation (IOF) suggested that [[postmenopausal]] women and men age 50 and older presenting with the following should be considered for treatment: | ||
** A [[hip]] or [[vertebral fracture]] (clinically apparent or found on [[vertebral]] imaging). There are abundant data that patients with [[spine]] and [[hip fractures]] will have reduced fracture risk if treated with [[pharmacologic]] [[therapy]]. This is true for [[fracture]] patients with [[Bone mineral density|BMD]] in both the low [[bone mass]] and [[osteoporosis]] range . In patients with a [[Hip Fractures|hip]] or [[spine]] [[fracture]], the T-score is not as important as the [[fracture]] itself in predicting [[future]] risk of [[fracture]] and antifracture efficacy from treatment. | ** A [[hip]] or [[vertebral fracture]] (clinically apparent or found on [[vertebral]] imaging). There are abundant data that patients with [[spine]] and [[hip fractures]] will have reduced fracture risk if treated with [[pharmacologic]] [[therapy]]. This is true for [[fracture]] patients with [[Bone mineral density|BMD]] in both the low [[bone mass]] and [[osteoporosis]] range . In patients with a [[Hip Fractures|hip]] or [[spine]] [[fracture]], the T-score is not as important as the [[fracture]] itself in predicting [[future]] risk of [[fracture]] and antifracture efficacy from treatment. | ||
** T-score ≤−2.5 at the [[femoral neck]], total [[hip]], or [[lumbar spine]]. There is abundant evidence that the elevated risk of [[fracture]] in patients with [[osteoporosis]] by [[Bone mineral density|BMD]] is reduced with [[pharmacotherapy]]. | ** T-score ≤−2.5 at the [[femoral neck]], total [[hip]], or [[lumbar spine]]. There is abundant evidence that the elevated risk of [[fracture]] in patients with [[osteoporosis]] by [[Bone mineral density|BMD]] is reduced with [[pharmacotherapy]]. | ||
** Low [[bone mass]] (T-score between −1.0 and −2.5 at the [[femoral neck]] or [[lumbar spine]]) and a 10-year probability of a [[hip fracture]] ≥3 % or a 10-year probability of a major [[osteoporosis]]-related [[fracture]] ≥20 % based on the US adapted WHO algorithm.<ref name="Cosmande Beur2014">{{cite journal|last1=Cosman|first1=F.|last2=de Beur|first2=S. J.|last3=LeBoff|first3=M. S.|last4=Lewiecki|first4=E. M.|last5=Tanner|first5=B.|last6=Randall|first6=S.|last7=Lindsay|first7=R.|title=Clinician’s Guide to Prevention and Treatment of Osteoporosis|journal=Osteoporosis International|volume=25|issue=10|year=2014|pages=2359–2381|issn=0937-941X|doi=10.1007/s00198-014-2794-2}}</ref> | ** Low [[bone mass]] (T-score between −1.0 and −2.5 at the [[femoral neck]] or [[lumbar spine]]) and a 10-year probability of a [[hip fracture]] ≥3 % or a 10-year probability of a major [[osteoporosis]]-related [[fracture]] ≥20 % based on the US adapted WHO algorithm.<ref name="Cosmande Beur2014">{{cite journal|last1=Cosman|first1=F.|last2=de Beur|first2=S. J.|last3=LeBoff|first3=M. S.|last4=Lewiecki|first4=E. M.|last5=Tanner|first5=B.|last6=Randall|first6=S.|last7=Lindsay|first7=R.|title=Clinician’s Guide to Prevention and Treatment of Osteoporosis|journal=Osteoporosis International|volume=25|issue=10|year=2014|pages=2359–2381|issn=0937-941X|doi=10.1007/s00198-014-2794-2}}</ref> | ||
* There is no established [[medical]] or [[surgical]] therapy for juvenile [[osteoporosis]]. In some cases, no treatment may be needed because the condition usually | * There is no established [[medical]] or [[surgical]] therapy for juvenile [[osteoporosis]]. In some cases, no treatment may be needed because the condition usually resolves spontaneously. However, early diagnosis of juvenile [[osteoporosis]] is important so that steps can be taken to protect the child’s [[spine]] and other [[bones]] from [[fracture]] until remission occurs. These steps may include [[physical therapy]], using [[crutches]], avoiding unsafe weight-bearing activities, and other supportive care. A well-balanced diet rich in [[calcium]] and [[vitamin D]] is also important. In severe, long-lasting cases of juvenile [[osteoporosis]], [[bisphosphonates]], have been given to children experimentally.<ref name="urlJuvenile Osteoporosis">{{cite web |url=https://www.niams.nih.gov/health_info/bone/Bone_Health/Juvenile/juvenile_osteoporosis.asp |title=Juvenile Osteoporosis |format= |work= |accessdate=}}</ref> | ||
=== Medical therapy options === | === Medical therapy options === | ||
Medications can be classified into<ref name="pmid37130601">{{cite journal| author=Händel MN, Cardoso I, von Bülow C, Rohde JF, Ussing A, Nielsen SM | display-authors=etal| title=Fracture risk reduction and safety by osteoporosis treatment compared with placebo or active comparator in postmenopausal women: systematic review, network meta-analysis, and meta-regression analysis of randomised clinical trials. | journal=BMJ | year= 2023 | volume= 381 | issue= | pages= e068033 | pmid=37130601 | doi=10.1136/bmj-2021-068033 | pmc=10152340 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=37130601 }} </ref><ref name="pmid36592456">{{cite journal| author=Qaseem A, Hicks LA, Etxeandia-Ikobaltzeta I, Shamliyan T, Cooney TG, Clinical Guidelines Committee of the American College of Physicians | display-authors=etal| title=Pharmacologic Treatment of Primary Osteoporosis or Low Bone Mass to Prevent Fractures in Adults: A Living Clinical Guideline From the American College of Physicians. | journal=Ann Intern Med | year= 2023 | volume= 176 | issue= 2 | pages= 224-238 | pmid=36592456 | doi=10.7326/M22-1034 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=36592456 }} </ref>: | |||
* antiresorptive drugs (selective estrogen receptor modulators, bisphosphonates, and denosumab) | |||
* anabolic treatments (romosozumab and parathyroid hormone receptor agonists) | |||
'''1 Stage 1 - Osteoporosis''' | '''1 Stage 1 - Osteoporosis''' | ||
* 1. | * 1.1 '''Improving bone mineral density (BMD)''' | ||
** 1.1. | ** 1.1.1 '''Adult''' | ||
*** Preferred regimen (1): | *** Preferred regimen (1): [[Alendronate]] 70 mg [[per os|PO]] weekly | ||
*** Preferred regimen (2): | *** Preferred regimen (2): [[Risedronate]] 35 mg [[per os|PO]] weekly OR 150 mg [[per os|PO]] monthly | ||
*** Preferred regimen (3): | *** Preferred regimen (3): [[Ibandronate]] 150 mg [[per os|PO]] monthly OR 3 mg [[IV]] every 3 months | ||
*** Preferred regimen (4): | *** Preferred regimen (4): [[Zoledronic acid]] 5 mg [[IV]] annually | ||
*** Alternative regimen (1): | *** Alternative regimen (1): [[Raloxifene]] 60 mg [[per os|PO]] daily | ||
*** Alternative regimen (2): | *** Alternative regimen (2): [[Denosumab]] 60 mg [[subcutaneous|SC]] every 6 months | ||
*** Alternative regimen (3): | *** Alternative regimen (3): Romosozumab 210 mg [[subcutaneous|SC]] monthly | ||
*** Alternative regimen (4): | *** Alternative regimen (4): [[Teriparatide]] 20 mcg [[subcutaneous|SC]] daily, approved for less than 2 years use | ||
*** Alternative regimen (5): | *** Alternative regimen (5): Abaloparatide 80 mcg [[subcutaneous|SC]] daily, approved for less than 2 years use | ||
*** Alternative regimen ( | *** Alternative regimen (6): [[Calcitonin]] 100 units [[subcutaneous|SC]] daily OR 200 units intranasal daily | ||
==== Anti-fracture efficacy of approved treatments for postmenopausal women with osteoporosis when given with calcium and vitamin D<ref name="pmid25182228" /> ==== | ==== Anti-fracture efficacy of approved treatments for postmenopausal women with osteoporosis when given with calcium and vitamin D<ref name="pmid25182228" /> ==== | ||
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|Highly effective | |Highly effective | ||
|} | |} | ||
'''1 Stage 1 - Osteoporosis''' | |||
* 1.1 '''Improving bone mineral density (BMD)''' | |||
** 1.1.2 '''Children and Adolescent''' | |||
** Doses are under studying and evaluation. | |||
*** Preferred regimen (1): [[Alendronate]] weekly | |||
*** Preferred regimen (2): [[Risedronate]] weekly OR monthly | |||
*** Preferred regimen (3): [[Ibandronate]] monthly OR every 3 months | |||
*** Alternative regimen (1): [[Zoledronic acid]] annually | |||
* Treatment options for children with low bone mass and [[fractures]] are more limited than in adults, underscoring the importance of accurate [[skeletal]] assessments. General measures to address [[skeletal]] risk factors are safe and appropriate first steps for all patients. All strategies to optimize [[bone]] health should be considered. [[Calcium]] intake should meet current recommendations of : | |||
** 500 mg for children 1 to 3 years of age, | |||
** 800 mg for children 4 to 8 years of age, | |||
** 1300 mg for children and adolescents 9 to 18 years of age. | |||
* Routine screening of [[vitamin D]] levels is not indicated in healthy youth. However, the adequacy of total body [[vitamin D]] stores should be assessed in youth at risk of [[bone]] fragility by measuring serum concentrations of [[25-hydroxy vitamin D]]. Concentrations of at least '''''20 ng/mL (50 nmol/L''''') have been recommended for healthy children, but some experts aim for a serum [[25-hydroxy vitamin D]] concentration '''''>30 ng/mL''''' in populations at increased risk of [[fracture]]. | |||
* Weight-bearing activity should be encouraged, and even short periods of high-intensity exercise (eg, jumping 10 minutes/ day, 3 times/week) have produced measurable gains in [[bone mass]]. The childhood and teenage years appear to be of particular importance for [[bone]] accretion. The Iowa Bone Development Study (a prospective cohort study) showed 10% to 16% greater hip BMC and 8% greater hip areal [[Bone mineral density|BMD]] in participants who accumulated the greatest amount of activity from childhood through adolescence (12-year follow-up).<ref name="JanzLetuchy2014">{{cite journal|last1=Janz|first1=Kathleen F.|last2=Letuchy|first2=Elena M.|last3=Francis|first3=Shelby L.|last4=Metcalf|first4=Kristen M.|last5=Burns|first5=Trudy L.|last6=Levy|first6=Steven M.|title=Objectively Measured Physical Activity Predicts Hip and Spine Bone Mineral Content in Children and Adolescents Ages 5–15 Years: Iowa Bone Development Study|journal=Frontiers in Endocrinology|volume=5|year=2014|issn=1664-2392|doi=10.3389/fendo.2014.00112}}</ref> | |||
*For patients with limited mobility, reducing immobility through [[physical therapy]] or the use of vibrating platforms can be helpful. Reducing inflammation, under-nutrition, or [[hormone]] imbalances is necessary. In children with [[inflammatory bowel disease]], study showed that a reduction in inflammation through the use of anti–[[Tumor necrosis factor alpha|tumor necrosis factor α]] therapy led to appreciable differences in [[bone]] structure and density. If general measures fail to prevent further [[bone loss]] and [[fracture]], [[pharmacologic]] therapy may be considered. None of the drugs used to treat [[bone]] fragility in the elderly have yet been approved by the [[Food and Drug Administration]] for [[pediatric]] use. Nevertheless, therapy with [[bisphosphonates]] is considered reasonable for children with moderate to severe [[osteogenesis imperfecta]] (2 or more fractures in a year or vertebral compression fractures). For secondary osteoporosis attributable to chronic [[disease]], [[bisphosphonates]] may be used on a compassionate basis to treat low-trauma [[fractures]] of the [[spine]] or [[extremities]]. When [[pharmacologic]] therapy is considered, referral to a specialist with expertise in pediatric bone disorders is advised.<ref name="pmid25919459">{{cite journal |vauthors=Griffin LM, Thayu M, Baldassano RN, DeBoer MD, Zemel BS, Denburg MR, Denson LA, Shults J, Herskovitz R, Long J, Leonard MB |title=Improvements in Bone Density and Structure during Anti-TNF-α Therapy in Pediatric Crohn's Disease |journal=J. Clin. Endocrinol. Metab. |volume=100 |issue=7 |pages=2630–9 |year=2015 |pmid=25919459 |pmc=4490303 |doi=10.1210/jc.2014-4152 |url=}}</ref><ref name="pmid16019729">{{cite journal |vauthors=Rauch F, Glorieux FH |title=Bisphosphonate treatment in osteogenesis imperfecta: which drug, for whom, for how long? |journal=Ann. Med. |volume=37 |issue=4 |pages=295–302 |year=2005 |pmid=16019729 |doi=10.1080/07853890510007386 |url=}}</ref> | |||
'''2 Stage 2 - Glucocorticoid induced osteoporosis''' | '''2 Stage 2 - Glucocorticoid induced osteoporosis''' | ||
* 2. | * 2.1 '''Improving bone mineral density (BMD)''' | ||
** 2.1. | ** 2.1.1 '''Adult''' | ||
*** Preferred regimen (1): | *** Preferred regimen (1): [[Alendronate]] 70 mg [[per os|PO]] weekly | ||
*** Preferred regimen (2): | *** Preferred regimen (2): [[Risedronate]] 35 mg [[per os|PO]] weekly OR 150 mg [[per os|PO]] monthly | ||
*** Preferred regimen (3): | *** Preferred regimen (3): [[Ibandronate]] 150 mg [[per os|PO]] monthly OR 3 mg [[IV]] every 3 months | ||
*** Preferred regimen (4): | *** Preferred regimen (4): [[Zoledronic acid]] 5 mg [[IV]] annually | ||
*** Alternative regimen (1): | *** Alternative regimen (1): [[Raloxifene]] 60 mg [[per os|PO]] daily | ||
*** Alternative regimen (2): | *** Alternative regimen (2): [[Denosumab]] 60 mg [[subcutaneous|SC]] every 6 months | ||
*** Alternative regimen (3): | *** Alternative regimen (3): Romosozumab 210 mg [[subcutaneous|SC]] monthly | ||
*** Alternative regimen (4): | *** Alternative regimen (4): [[Teriparatide]] 20 mcg [[subcutaneous|SC]] daily, approved for less than 2 years use | ||
*** Alternative regimen (5): | *** Alternative regimen (5): Abaloparatide 80 mcg [[subcutaneous|SC]] daily, approved for less than 2 years use | ||
*** Alternative regimen ( | *** Alternative regimen (6): [[Calcitonin]] 100 units [[subcutaneous|SC]] daily OR 200 units intranasal daily | ||
==== Recommendations for initial treatment for glucocorticoid induced osteoporosis in adults by American College of Rheumatology (ACR), 2017<ref name="BuckleyGuyatt2017">{{cite journal|last1=Buckley|first1=Lenore|last2=Guyatt|first2=Gordon|last3=Fink|first3=Howard A.|last4=Cannon|first4=Michael|last5=Grossman|first5=Jennifer|last6=Hansen|first6=Karen E.|last7=Humphrey|first7=Mary Beth|last8=Lane|first8=Nancy E.|last9=Magrey|first9=Marina|last10=Miller|first10=Marc|last11=Morrison|first11=Lake|last12=Rao|first12=Madhumathi|last13=Robinson|first13=Angela Byun|last14=Saha|first14=Sumona|last15=Wolver|first15=Susan|last16=Bannuru|first16=Raveendhara R.|last17=Vaysbrot|first17=Elizaveta|last18=Osani|first18=Mikala|last19=Turgunbaev|first19=Marat|last20=Miller|first20=Amy S.|last21=McAlindon|first21=Timothy|title=2017 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis|journal=Arthritis & Rheumatology|volume=69|issue=8|year=2017|pages=1521–1537|issn=23265191|doi=10.1002/art.40137}}</ref> ==== | ==== Recommendations for initial treatment for glucocorticoid induced osteoporosis in adults by American College of Rheumatology (ACR), 2017<ref name="BuckleyGuyatt2017">{{cite journal|last1=Buckley|first1=Lenore|last2=Guyatt|first2=Gordon|last3=Fink|first3=Howard A.|last4=Cannon|first4=Michael|last5=Grossman|first5=Jennifer|last6=Hansen|first6=Karen E.|last7=Humphrey|first7=Mary Beth|last8=Lane|first8=Nancy E.|last9=Magrey|first9=Marina|last10=Miller|first10=Marc|last11=Morrison|first11=Lake|last12=Rao|first12=Madhumathi|last13=Robinson|first13=Angela Byun|last14=Saha|first14=Sumona|last15=Wolver|first15=Susan|last16=Bannuru|first16=Raveendhara R.|last17=Vaysbrot|first17=Elizaveta|last18=Osani|first18=Mikala|last19=Turgunbaev|first19=Marat|last20=Miller|first20=Amy S.|last21=McAlindon|first21=Timothy|title=2017 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis|journal=Arthritis & Rheumatology|volume=69|issue=8|year=2017|pages=1521–1537|issn=23265191|doi=10.1002/art.40137}}</ref> ==== | ||
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{{Family tree | | | | | | | | |`|-|-|v|-|-|'| | | | |}} | {{Family tree | | | | | | | | |`|-|-|v|-|-|'| | | | |}} | ||
{{Family tree | | | | | | | | |,|-|-|^|-|-|.| | | | |}} | {{Family tree | | | | | | | | |,|-|-|^|-|-|.| | | | |}} | ||
{{Family tree | | | | | | | | A01 | | | | A02 | | | |A01='''Treat with an oral [[bisphosphonate]]'''<br> <br>Second-line therapy: '''[[teriparatide]]''' <br> <br>Other suggested therapies (in order of preference)<br>for high risk woman for whom the previous drugs are not appropriate:<br> <br>IV [[bisphosphonate]]<br> [[Denosumab]]|A02='''Treat with an oral [[bisphosphonate]]'''<br>Other suggested therapies (in order of preference): <br> <br>IV [[bisphosphonate]]<br> [[Teriparatide]]<br> [[Denosumab]]<br> [[Raloxifen]] for [[postmenopausal]] women if no other therapy is available}} | {{Family tree | | | | | | | | A01 | | | | A02 | | | |A01='''Treat with an oral [[bisphosphonate]]'''<br> <br>Second-line therapy: '''[[teriparatide]]''' <br> <br>Other suggested therapies (in order of preference)<br>for high risk woman for whom the previous drugs are not appropriate:<br> <br>[[IV]] [[bisphosphonate]]<br> [[Denosumab]]|A02='''Treat with an oral [[bisphosphonate]]'''<br>Other suggested therapies (in order of preference): <br> <br>[[IV]] [[bisphosphonate]]<br> [[Teriparatide]]<br> [[Denosumab]]<br> [[Raloxifen]] for [[postmenopausal]] women if no other therapy is available}} | ||
{{Family tree/end}} | {{Family tree/end}} | ||
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=== '''Bisphosphonates''' === | === '''Bisphosphonates''' === | ||
[[Bisphosphonates]] are the '''''first line''''' treatment for [[osteoporosis]] [[disease]]. They are not indicated in people with severe [[renal function impairment]]; thus, it is important to check [[renal function]] and serum [[creatinine]] before [[prescription]]. These drugs | [[Bisphosphonates]] are the '''''first line''''' treatment for [[osteoporosis]] [[disease]]. They are not indicated in people with severe [[renal function impairment]]; thus, it is important to check [[renal function]] and serum [[creatinine]] before [[prescription]]. These drugs need to be taken [[Orally ingested|orally]] with large amount of water and not laying down until two hours following consumption, due to high risk of [[esophagitis]]. Rare but serious side effects may include [[osteonecrosis of the jaw]] and atypical [[femoral]] [[Bone fracture|fractures]]. | ||
* [[Alendronate|'''Alendronate''']]: It is frequently used to treat [[osteoporosis]] in men, [[postmenopausal]] women, and also in [[corticosteroid]]-induced [[osteoporosis]]. Alendronate reduces the incidence of spine and hip fractures by about 50 % over 3 years in patients with a prior vertebral fracture or in patients who have osteoporosis at the hip site. It reduces the incidence of vertebral fractures by 48 % over 3 years in patients without a prior vertebral fracture.<ref name="Cosmande Beur2014" /> | * [[Alendronate|'''Alendronate''']]: It is frequently used to treat [[osteoporosis]] in men, [[postmenopausal]] women, and also in [[corticosteroid]]-induced [[osteoporosis]]. Alendronate reduces the incidence of spine and hip fractures by about 50 % over 3 years in patients with a prior vertebral fracture or in patients who have osteoporosis at the hip site. It reduces the incidence of vertebral fractures by 48 % over 3 years in patients without a prior vertebral fracture.<ref name="Cosmande Beur2014" /> | ||
** The dosing is 70mg weekly per oral. | ** The dosing is 70mg weekly per oral. | ||
** [[Alendronate]] reduces [[Hip (anatomy)|hip]], [[vertebral]], and non-[[vertebral]] [[Osteoporosis|osteoporotic]] [[fractures]]. | ** [[Alendronate]] reduces [[Hip (anatomy)|hip]], [[vertebral]], and non-[[vertebral]] [[Osteoporosis|osteoporotic]] [[fractures]]. | ||
* [[Risedronate|'''Risedronate''']]: It is also used to treat [[Paget's disease]]. [[Risedronate]] decreases the [[Bone loss|bone mass loss]]. Also available in delayed release forms. | * [[Risedronate|'''Risedronate''']]: It is also used to treat [[Paget's disease]]. [[Risedronate]] decreases the [[Bone loss|bone mass loss]]. Also available in delayed release forms. Risendronate reduces the incidence of vertebral fractures by 41 to 49 % and nonvertebral fractures by 36 % over 3 years, with significant risk reduction occurring within 1 year of treatment in patients with a prior vertebral fracture.<ref name="pmid10527181">{{cite journal |vauthors=Harris ST, Watts NB, Genant HK, McKeever CD, Hangartner T, Keller M, Chesnut CH, Brown J, Eriksen EF, Hoseyni MS, Axelrod DW, Miller PD |title=Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. Vertebral Efficacy With Risedronate Therapy (VERT) Study Group |journal=JAMA |volume=282 |issue=14 |pages=1344–52 |year=1999 |pmid=10527181 |doi= |url=}}</ref> | ||
** The dosing is 35mg weekly or 150mg monthly per oral. | ** The dosing is 35mg weekly or 150mg monthly per oral. | ||
** [[Risedronate]] reduces [[vertebral]] [[fractures]]. | ** [[Risedronate]] reduces [[vertebral]] [[fractures]]. | ||
* [[Ibandronate|'''Ibandronate''']]: It is used to treat osteoporosis only in [[postmenopausal]] women. Ibandronate reduces the incidence of vertebral fractures by about 50 % over 3 years, but reduction in risk of | * [[Ibandronate|'''Ibandronate''']]: It is used to treat osteoporosis only in [[postmenopausal]] women. Ibandronate reduces the incidence of [[vertebral fractures]] by about 50 % over 3 years, but the reduction in risk of non-vertebral fracture with ibandronate has not been documented.<ref name="pmid15231010">{{cite journal |vauthors=Chesnut CH, Skag A, Christiansen C, Recker R, Stakkestad JA, Hoiseth A, Felsenberg D, Huss H, Gilbride J, Schimmer RC, Delmas PD |title=Effects of oral ibandronate administered daily or intermittently on fracture risk in postmenopausal osteoporosis |journal=J. Bone Miner. Res. |volume=19 |issue=8 |pages=1241–9 |year=2004 |pmid=15231010 |doi=10.1359/JBMR.040325 |url=}}</ref> | ||
** The dosing is 150mg monthly per oral | ** The dosing is 150mg monthly per oral, or 3mg every 3 months through [[Intravenous|intravenous (IV)]] route. | ||
** Regarding that [[Ibandronate]] only reduced [[vertebral]] [[fractures]] and there is no evidence of non-[[vertebral]] fractures improvement, it is rarely prescribed. | ** Regarding that [[Ibandronate]] only reduced [[vertebral]] [[fractures]] and there is no evidence of non-[[vertebral]] fractures improvement, it is rarely prescribed. | ||
* [[Zoledronic acid|'''Zoledronic''' '''acid''']]: It is also used for [[bone]] | * [[Zoledronic acid|'''Zoledronic''' '''acid''']]: It is also used for [[bone]] destruction due to [[Paget's disease]], [[multiple myeloma]], and [[metastatic]] [[bone tumors]]. Most potent [[bisphosphonate]] that has a higher risk of [[osteonecrosis of the jaw]]. Zoledronic acid reduces the incidence of [[vertebral fractures]] by 70% (with the significant reduction at 1 year), [[hip fractures]] by 41 %, and nonvertebral fractures by 25 % over 3 years in patients with osteoporosis defined by prevalent [[vertebral fractures]] and osteoporosis by BMD of the hip.<ref name="pmid17476007">{{cite journal |vauthors=Black DM, Delmas PD, Eastell R, Reid IR, Boonen S, Cauley JA, Cosman F, Lakatos P, Leung PC, Man Z, Mautalen C, Mesenbrink P, Hu H, Caminis J, Tong K, Rosario-Jansen T, Krasnow J, Hue TF, Sellmeyer D, Eriksen EF, Cummings SR |title=Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis |journal=N. Engl. J. Med. |volume=356 |issue=18 |pages=1809–22 |year=2007 |pmid=17476007 |doi=10.1056/NEJMoa067312 |url=}}</ref> | ||
** The dosing is 5mg annually through [[Intravenous therapy|IV]] route. | ** The dosing is 5mg annually through [[Intravenous therapy|IV]] route. | ||
** [[Zoledronate]] reduces [[hip]], [[vertebral]], and non-[[vertebral]] [[Osteoporosis|osteoporotic]] [[fractures]]. Common [[adverse effects]] are [[flu]]-like symptoms and [[bone]] pain, especially presented with first dose. | ** [[Zoledronate]] reduces [[hip]], [[vertebral]], and non-[[vertebral]] [[Osteoporosis|osteoporotic]] [[fractures]]. Common [[adverse effects]] are [[flu]]-like symptoms and [[bone]] pain, especially presented with the first dose. | ||
===National Osteoporosis Guideline Group (NOGG) algorithm for long term bisphosphonate therapy monitoring<ref name="pmid25182228">{{cite journal| author=Cosman F, de Beur SJ, LeBoff MS, Lewiecki EM, Tanner B, Randall S et al.| title=Clinician's Guide to Prevention and Treatment of Osteoporosis. | journal=Osteoporos Int | year= 2014 | volume= 25 | issue= 10 | pages= 2359-81 | pmid=25182228 | doi=10.1007/s00198-014-2794-2 | pmc=4176573 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25182228 }} </ref>=== | ===National Osteoporosis Guideline Group (NOGG) algorithm for long term bisphosphonate therapy monitoring<ref name="pmid25182228">{{cite journal| author=Cosman F, de Beur SJ, LeBoff MS, Lewiecki EM, Tanner B, Randall S et al.| title=Clinician's Guide to Prevention and Treatment of Osteoporosis. | journal=Osteoporos Int | year= 2014 | volume= 25 | issue= 10 | pages= 2359-81 | pmid=25182228 | doi=10.1007/s00198-014-2794-2 | pmc=4176573 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25182228 }} </ref>=== | ||
{{Family tree/start}} | <span style="font-size:85%">'''Abbreviations:''' '''FRAX:''' Fracture risk assessment tool</span><ref name="urlwww.sheffield.ac.uk">{{cite web |url=https://www.sheffield.ac.uk/FRAX/tool.jsp |title=www.sheffield.ac.uk |format= |work= |accessdate=}}</ref>{{Family tree/start}} | ||
{{Family tree | | | | | | A01 | | | | | | | | |A01=Advise<br>3 years '''[[zoledronic acid]]'''<br>or<br>5 years '''other [[bisphosphonates]]'''<br> (follow up at 3/12 to discuss treatment issues)}} | {{Family tree | | | | | | A01 | | | | | | | | |A01=Advise<br>3 years '''[[zoledronic acid]]'''<br>or<br>5 years '''other [[bisphosphonates]]'''<br> (follow up at 3/12 to discuss treatment issues)}} | ||
{{Family tree | | | | | | |!| | | | | | | | | | | | }} | {{Family tree | | | | | | |!| | | | | | | | | | | | }} | ||
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==== Receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitor ==== | ==== Receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitor ==== | ||
* '''[[Denosumab]]:''' Human [[monoclonal antibody]] designed to inhibit [[RANKL]] ([[RANK]] ligand), a [[protein]] that acts as the primary [[Signal (biology)|signal]] for [[bone]] removal. It is used to treat [[ | * '''[[Denosumab]]:''' Human [[monoclonal antibody]] designed to inhibit [[RANKL]] ([[RANK]] ligand), a [[protein]] that acts as the primary [[Signal (biology)|signal]] for [[bone]] removal. It is used to treat [[osteoporosis]] in older men and [[postmenopausal]] women. | ||
** The dosing is 60mg subcutaneous every 6 months. | ** The dosing is 60mg [[subcutaneous]] every 6 months. | ||
** [[Denosumab]] reduces [[hip]], [[vertebral]], and non-[[vertebral]] [[Osteoporosis|osteoporotic]] [[fractures]]. | ** [[Denosumab]] reduces [[hip]], [[vertebral]], and non-[[vertebral]] [[Osteoporosis|osteoporotic]] [[fractures]]. | ||
** The major side effects are [[eczema]] and [[nausea]].<ref name="pmid227768602">{{cite journal |vauthors=McClung MR, Lewiecki EM, Geller ML, Bolognese MA, Peacock M, Weinstein RL, Ding B, Rockabrand E, Wagman RB, Miller PD |title=Effect of denosumab on bone mineral density and biochemical markers of bone turnover: 8-year results of a phase 2 clinical trial |journal=Osteoporos Int |volume=24 |issue=1 |pages=227–35 |year=2013 |pmid=22776860 |pmc=3536967 |doi=10.1007/s00198-012-2052-4 |url=}}</ref> | ** The major side effects are [[eczema]] and [[nausea]].<ref name="pmid227768602">{{cite journal |vauthors=McClung MR, Lewiecki EM, Geller ML, Bolognese MA, Peacock M, Weinstein RL, Ding B, Rockabrand E, Wagman RB, Miller PD |title=Effect of denosumab on bone mineral density and biochemical markers of bone turnover: 8-year results of a phase 2 clinical trial |journal=Osteoporos Int |volume=24 |issue=1 |pages=227–35 |year=2013 |pmid=22776860 |pmc=3536967 |doi=10.1007/s00198-012-2052-4 |url=}}</ref> | ||
*'''Romosozumab''': Human [[monoclonal antibody]] designed to [[sclerostin]], blocking [[protein]] of canonical [[Wnt signaling pathway|Wnt signaling bone formation pathway.]] It is used to prevent [[Osteoporosis|osteoporotic]] [[fractures]] in [[postmenopausal]] women. | *'''Romosozumab''': Human [[monoclonal antibody]] designed to inhibit [[sclerostin]], a blocking [[protein]] of canonical [[Wnt signaling pathway|Wnt signaling bone formation pathway.]] It is used to prevent [[Osteoporosis|osteoporotic]] [[fractures]] in [[postmenopausal]] women. | ||
**The dosing is 210mg [[subcutaneous]] monthly. | **The dosing is 210mg [[subcutaneous]] monthly. | ||
**Romosozumab reduces [[vertebral fractures]].<ref name="pmid28064540">{{cite journal |vauthors=Bandeira L, Lewiecki EM, Bilezikian JP |title=Romosozumab for the treatment of osteoporosis |journal=Expert Opin Biol Ther |volume=17 |issue=2 |pages=255–263 |year=2017 |pmid=28064540 |doi=10.1080/14712598.2017.1280455 |url=}}</ref> | **Romosozumab reduces [[vertebral fractures]].<ref name="pmid28064540">{{cite journal |vauthors=Bandeira L, Lewiecki EM, Bilezikian JP |title=Romosozumab for the treatment of osteoporosis |journal=Expert Opin Biol Ther |volume=17 |issue=2 |pages=255–263 |year=2017 |pmid=28064540 |doi=10.1080/14712598.2017.1280455 |url=}}</ref> | ||
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==== Parathyroid hormone and related peptide analogs ==== | ==== Parathyroid hormone and related peptide analogs ==== | ||
*'''[[Teriparatide]]''': | *'''[[Teriparatide]]''': The human [[recombinant]] [[parathyroid hormone]] used to treat the [[postmenopausal]] women with [[osteoporosis]] at high risk of [[fracture]] or to increase [[bone]] mass in men with [[osteoporosis]]. | ||
*Usually, it is used in patients who cannot tolerate the oral [[bisphosphonates]]. | *Usually, it is used in patients who cannot tolerate the oral [[bisphosphonates]]. | ||
**It is also approved for [[corticosteroid]] induced [[osteoporosis]]. | **It is also approved for [[corticosteroid]] induced [[osteoporosis]]. | ||
**The dosing is 20mcg [[subcutaneous]] daily, approved for less than 2 years use. | **The dosing is 20mcg [[subcutaneous]] daily, approved for less than 2 years use. | ||
**[[Teriparatide]] reduces [[vertebral]] and non-[[vertebral]] [[fractures]], but not | **[[Teriparatide]] reduces [[vertebral]] and non-[[vertebral]] [[fractures]], but not [[hip fracture]]. | ||
**Common side effects include [[nausea]], [[hypercalcemia]], and [[hypercalciuria]]. However, patients with previous [[radiation therapy]], [[paget's disease]], or young patients should avoid this medication. | **Common side effects include [[nausea]], [[hypercalcemia]], and [[hypercalciuria]]. However, patients with previous [[radiation therapy]], [[paget's disease]], or young patients should avoid this medication. | ||
*'''Abaloparatide''': | *'''Abaloparatide''': The human [[recombinant]] [[parathyroid hormone]] used to treat the [[postmenopausal]] women with [[osteoporosis]] at high risk of [[fracture]] or to increase [[bone]] mass in men with [[osteoporosis]]. | ||
**It has a shorter duration of action than [[teriparatide]]. | **It has a shorter duration of action than [[teriparatide]]. | ||
**The dosing is 80mcg [[subcutaneous]] daily, approved for less than 2 years use. | **The dosing is 80mcg [[subcutaneous]] daily, approved for less than 2 years use. | ||
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==== Calcitonin ==== | ==== Calcitonin ==== | ||
* [[Calcitonin]] is a hormone that | * [[Calcitonin]] is a hormone that inhibits the function of [[osteoclasts]] and resulting in growing [[bone mass]]. On the other hand, it can stimulate the [[osteoblast]] and also inhibit [[sclerostin]] production. | ||
* It is used for [[postmenopausal]] women with [[osteoporosis]]. | * It is used for [[postmenopausal]] women with [[osteoporosis]]. | ||
* The dosing is 100units [[subcutaneous]] daily; or 200units [[Intranasal route|intranasal]] daily. | * The dosing is 100units [[subcutaneous]] daily; or 200units [[Intranasal route|intranasal]] daily. | ||
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=== Non-FDA-approved drugs for osteoporosis === | === Non-FDA-approved drugs for osteoporosis === | ||
Nonapproved agents include: | Nonapproved agents include: | ||
* '''Calcitriol''': This synthetic [[vitamin D]] | * '''Calcitriol''': This synthetic [[vitamin D]] analog, which promotes [[calcium]] absorption, has been approved by the [[FDA]] for managing [[hypocalcemia]] and metabolic [[bone]] [[disease]] in renal [[dialysis]] patients. It is also approved for use in [[hypoparathyroidism]], both surgical and [[idiopathic]], and [[pseudohypoparathyroidism]]. No reliable data demonstrate a reduction of risk for osteoporotic [[fracture]]. | ||
* '''Genistein''': An [[isoflavone]] [[phytoestrogen]] which is the main ingredient in the prescription “medical food” product Fosteum® and generally regarded as safe by the FDA. [[Genistein]] may benefit [[bone]] health in [[postmenopausal]] women but more data are needed to fully understand its effects on [[bone]] health and [[fracture]] risk. | * '''Genistein''': An [[isoflavone]] [[phytoestrogen]] which is the main ingredient in the prescription “medical food” product Fosteum® and generally regarded as safe by the FDA. [[Genistein]] may benefit [[bone]] health in [[postmenopausal]] women but more data are needed to fully understand its effects on [[bone]] health and [[fracture]] risk. | ||
* '''Other bisphosphonates (etidronate, pamidronate, tiludronate)''': These medications vary chemically from [[alendronate]], [[ibandronate]], [[risedronate]], and [[zoledronic acid]] but are in the same drug class. At this time, none is approved for prevention or treatment of [[osteoporosis]]. Most of these medications are currently approved for other conditions (e.g., [[Paget’s disease]], [[hypercalcemia]] of [[malignancy]], [[myositis ossificans]]). | * '''Other bisphosphonates (etidronate, pamidronate, tiludronate)''': These medications vary chemically from [[alendronate]], [[ibandronate]], [[risedronate]], and [[zoledronic acid]] but are in the same drug class. At this time, none is approved for prevention or treatment of [[osteoporosis]]. Most of these medications are currently approved for other conditions (e.g., [[Paget’s disease]], [[hypercalcemia]] of [[malignancy]], [[myositis ossificans]]). | ||
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==References== | ==References== | ||
{{Reflist|2}} | {{Reflist|2}} | ||
| |||
[[Category:Medicine]] | |||
[[Category:Endocrinology]] | [[Category:Endocrinology]] | ||
[[Category: | [[Category:Up-To-Date]] | ||
Latest revision as of 22:47, 6 May 2023
Osteoporosis Microchapters |
Diagnosis |
---|
Treatment |
Medical Therapy |
Case Studies |
Osteoporosis medical therapy On the Web |
American Roentgen Ray Society Images of Osteoporosis medical therapy |
Risk calculators and risk factors for Osteoporosis medical therapy |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Eiman Ghaffarpasand, M.D. [2]
Overview
The mainstay of treatment in primary osteoporosis is based on life style modifications. Most of the time in high risk patients and people with past history of osteoporotic fracture, medical therapy is necessary. Bisphosphonates are the first line treatment for osteoporosis. Raloxifene is the second line treatment of osteoporosis in postmenopausal women, for both treatment and prevention. Denosumab is a human monoclonal antibody designed to inhibit RANKL (RANK ligand), a protein that acts as the primary signal for bone removal. It is used to treat osteoporosis in older men and postmenopausal women. Teriparatide and Abaloparatide are human recombinant parathyroid hormones used to treat postmenopausal osteoporosis in women with high risk of fracture or to increase bone mass in men with osteoporosis.
Medical therapy
Fracture prevention medical therapy algorithm[1]
Strategies to prevent fractures and falls Recommend: • Dietary calcium 1200 mg/day Suggest: • Vitamin D (≥ 800–2000 IU/day) • Calcium supplement≤ 500 mg, if dietary calcium not met • Hip protectors • Multifactorial fall-prevention strategies: 1. Exercise (balance, strength and functional training) 2. Medication reviews (e.g., Beers criteria) 3. Assessment of environmental hazards 4. Use of assistive devices 5. Management of urinary incontinence | Fracture risk assessment on admission • Prior hip fracture? • Prior vertebral fracture? • More than one prior fracture (excluding hands, feet, ankles)? • Recent use of glucocorticoid and prior fracture (excluding hands, feet, ankles)? • Assessed as high risk for fracture and receiving fracture treatment before admission? • Vertebral fracture present? (if chest radiography ordered, screen for vertebral fractures) | ||||||||||||||||||||||||||||||||||||||||||
If patient has a fracture, reassess | |||||||||||||||||||||||||||||||||||||||||||
If "yes" to any of the above, patient is considered as high risk | |||||||||||||||||||||||||||||||||||||||||||
Recommend: Dietary calcium 1200 mg/day Vitamin D supplements (800–2000 IU/day) Calcium supplements ≤ 500 mg, if dietary calcium not met Hip protectors for mobile residents Suggest: Exercise program only as part of multifactorial fracture and fall prevention program | |||||||||||||||||||||||||||||||||||||||||||
Pharmacologic therapy not appropriate | No | Is patient expected to live > 1 year? | |||||||||||||||||||||||||||||||||||||||||
Yes | |||||||||||||||||||||||||||||||||||||||||||
Is CrCl > 30 mL/min? | |||||||||||||||||||||||||||||||||||||||||||
No | Yes | ||||||||||||||||||||||||||||||||||||||||||
Yes | Does patient have dysphagia? | ||||||||||||||||||||||||||||||||||||||||||
No | |||||||||||||||||||||||||||||||||||||||||||
For patients with CrCl 15–30 mL/min Recommend: • Denosumab (60 mg subcutaneously twice yearly) Remarks: • Monitor calcium levels, given higher risk of hypocalcemia • Bisphosphonate therapies are not recommended • Consider referral to specialist | Recommend: • Denosumab (60 mg subcutaneously twice yearly) • Zoledronic acid (5 mg IV once yearly) Suggest: • Teriparatide (20 mcg subcutaneously daily) | Recommend: • Alendronate (70 mg weekly) • Risedronate (35 mg weekly or 150 mg monthly) • Denosumab (60 mg subcutaneously twice yearly) • Zoledronic acid (5 mg IV once yearly) Suggest: • Teriparatide (20 mcg subcutaneously daily) | |||||||||||||||||||||||||||||||||||||||||
Most of the time in high risk patients and people with past history of osteoporotic fracture, medical therapy is necessary.[2]
Medical therapy purpose
- The primary most important goal for treatment of osteoporosis is to reduce longtime fracture risk in patients. Increasing bone mineral density (BMD) in response to the treatment is far less important than improvement of clinical aspects of osteoporosis, i.e., osteoporotic fracture. Therefore, most of the drugs efficacy is measured by the extent it can improve the fracture risk.[3]
- During the treatment, if a single fracture happens, it may not necessarily reflect treatment failure; and may need to start alternative treatments or patient referral to specialist.[4]
- Calcium and vitamin D supplementation have been found to be effective in reducing the long term fracture risk, significantly. In order to suggest the people to use vitamin D and calcium supplements, first the physician has to become sure that patient is not able to obtain the nutrients through daily intake. The available supplemental ions of calcium include calcium carbonate and calcium citrate; and vitamin D3.[5]
Medical therapy candidates
- The National osteoporosis foundation (NOF) has declared following prescription for osteoporosis treatment:
- Elder men and postmenopausal women with past history of osteoporotic fracture
- Elder man and postmenopausal women with BMD-identified osteoporosis (T-score ≤ -2.5 SD)
- Elder man and postmenopausal women with -1.0 > T-score > -2.5 SD with high risk of osteoporotic fracture
- Men with hypogonadism in whom testosterone therapy is contraindicated[4]
- The International osteoporosis foundation (IOF) suggested that postmenopausal women and men age 50 and older presenting with the following should be considered for treatment:
- A hip or vertebral fracture (clinically apparent or found on vertebral imaging). There are abundant data that patients with spine and hip fractures will have reduced fracture risk if treated with pharmacologic therapy. This is true for fracture patients with BMD in both the low bone mass and osteoporosis range . In patients with a hip or spine fracture, the T-score is not as important as the fracture itself in predicting future risk of fracture and antifracture efficacy from treatment.
- T-score ≤−2.5 at the femoral neck, total hip, or lumbar spine. There is abundant evidence that the elevated risk of fracture in patients with osteoporosis by BMD is reduced with pharmacotherapy.
- Low bone mass (T-score between −1.0 and −2.5 at the femoral neck or lumbar spine) and a 10-year probability of a hip fracture ≥3 % or a 10-year probability of a major osteoporosis-related fracture ≥20 % based on the US adapted WHO algorithm.[6]
- There is no established medical or surgical therapy for juvenile osteoporosis. In some cases, no treatment may be needed because the condition usually resolves spontaneously. However, early diagnosis of juvenile osteoporosis is important so that steps can be taken to protect the child’s spine and other bones from fracture until remission occurs. These steps may include physical therapy, using crutches, avoiding unsafe weight-bearing activities, and other supportive care. A well-balanced diet rich in calcium and vitamin D is also important. In severe, long-lasting cases of juvenile osteoporosis, bisphosphonates, have been given to children experimentally.[7]
Medical therapy options
Medications can be classified into[8][9]:
- antiresorptive drugs (selective estrogen receptor modulators, bisphosphonates, and denosumab)
- anabolic treatments (romosozumab and parathyroid hormone receptor agonists)
1 Stage 1 - Osteoporosis
- 1.1 Improving bone mineral density (BMD)
- 1.1.1 Adult
- Preferred regimen (1): Alendronate 70 mg PO weekly
- Preferred regimen (2): Risedronate 35 mg PO weekly OR 150 mg PO monthly
- Preferred regimen (3): Ibandronate 150 mg PO monthly OR 3 mg IV every 3 months
- Preferred regimen (4): Zoledronic acid 5 mg IV annually
- Alternative regimen (1): Raloxifene 60 mg PO daily
- Alternative regimen (2): Denosumab 60 mg SC every 6 months
- Alternative regimen (3): Romosozumab 210 mg SC monthly
- Alternative regimen (4): Teriparatide 20 mcg SC daily, approved for less than 2 years use
- Alternative regimen (5): Abaloparatide 80 mcg SC daily, approved for less than 2 years use
- Alternative regimen (6): Calcitonin 100 units SC daily OR 200 units intranasal daily
- 1.1.1 Adult
Anti-fracture efficacy of approved treatments for postmenopausal women with osteoporosis when given with calcium and vitamin D[10]
Vertebral fracture | Non-vertebral fracture | Hip fracture | |
---|---|---|---|
Alendronate | Highly effective | Highly effective | Highly effective |
Etidronate | Highly effective | Moderately effective | Not adequately evaluated |
Ibandronate | Highly effective | Highly effective | Not adequately evaluated |
Risedronate | Highly effective | Highly effective | Highly effective |
Zoledronic acid | Highly effective | Highly effective | Highly effective |
Denosumab | Highly effective | Highly effective | Highly effective |
Calcitriol | Highly effective | Moderately effective | Not adequately evaluated |
Raloxifene | Highly effective | Not adequately evaluated | Not adequately evaluated |
Strontium ranelate | Highly effective | Highly effective | Highly effective |
Teriparatide | Highly effective | Highly effective | Not adequately evaluated |
Recombinant human PTH (1-84) | Highly effective | Not adequately evaluated | Not adequately evaluated |
Hormone replacement therapy (HRT) | Highly effective | Highly effective | Highly effective |
1 Stage 1 - Osteoporosis
- 1.1 Improving bone mineral density (BMD)
- 1.1.2 Children and Adolescent
- Doses are under studying and evaluation.
- Preferred regimen (1): Alendronate weekly
- Preferred regimen (2): Risedronate weekly OR monthly
- Preferred regimen (3): Ibandronate monthly OR every 3 months
- Alternative regimen (1): Zoledronic acid annually
- Treatment options for children with low bone mass and fractures are more limited than in adults, underscoring the importance of accurate skeletal assessments. General measures to address skeletal risk factors are safe and appropriate first steps for all patients. All strategies to optimize bone health should be considered. Calcium intake should meet current recommendations of :
- 500 mg for children 1 to 3 years of age,
- 800 mg for children 4 to 8 years of age,
- 1300 mg for children and adolescents 9 to 18 years of age.
- Routine screening of vitamin D levels is not indicated in healthy youth. However, the adequacy of total body vitamin D stores should be assessed in youth at risk of bone fragility by measuring serum concentrations of 25-hydroxy vitamin D. Concentrations of at least 20 ng/mL (50 nmol/L) have been recommended for healthy children, but some experts aim for a serum 25-hydroxy vitamin D concentration >30 ng/mL in populations at increased risk of fracture.
- Weight-bearing activity should be encouraged, and even short periods of high-intensity exercise (eg, jumping 10 minutes/ day, 3 times/week) have produced measurable gains in bone mass. The childhood and teenage years appear to be of particular importance for bone accretion. The Iowa Bone Development Study (a prospective cohort study) showed 10% to 16% greater hip BMC and 8% greater hip areal BMD in participants who accumulated the greatest amount of activity from childhood through adolescence (12-year follow-up).[11]
- For patients with limited mobility, reducing immobility through physical therapy or the use of vibrating platforms can be helpful. Reducing inflammation, under-nutrition, or hormone imbalances is necessary. In children with inflammatory bowel disease, study showed that a reduction in inflammation through the use of anti–tumor necrosis factor α therapy led to appreciable differences in bone structure and density. If general measures fail to prevent further bone loss and fracture, pharmacologic therapy may be considered. None of the drugs used to treat bone fragility in the elderly have yet been approved by the Food and Drug Administration for pediatric use. Nevertheless, therapy with bisphosphonates is considered reasonable for children with moderate to severe osteogenesis imperfecta (2 or more fractures in a year or vertebral compression fractures). For secondary osteoporosis attributable to chronic disease, bisphosphonates may be used on a compassionate basis to treat low-trauma fractures of the spine or extremities. When pharmacologic therapy is considered, referral to a specialist with expertise in pediatric bone disorders is advised.[12][13]
2 Stage 2 - Glucocorticoid induced osteoporosis
- 2.1 Improving bone mineral density (BMD)
- 2.1.1 Adult
- Preferred regimen (1): Alendronate 70 mg PO weekly
- Preferred regimen (2): Risedronate 35 mg PO weekly OR 150 mg PO monthly
- Preferred regimen (3): Ibandronate 150 mg PO monthly OR 3 mg IV every 3 months
- Preferred regimen (4): Zoledronic acid 5 mg IV annually
- Alternative regimen (1): Raloxifene 60 mg PO daily
- Alternative regimen (2): Denosumab 60 mg SC every 6 months
- Alternative regimen (3): Romosozumab 210 mg SC monthly
- Alternative regimen (4): Teriparatide 20 mcg SC daily, approved for less than 2 years use
- Alternative regimen (5): Abaloparatide 80 mcg SC daily, approved for less than 2 years use
- Alternative regimen (6): Calcitonin 100 units SC daily OR 200 units intranasal daily
- 2.1.1 Adult
Recommendations for initial treatment for glucocorticoid induced osteoporosis in adults by American College of Rheumatology (ACR), 2017[14]
Calcium and vitamin D and life style modification | |||||||||||||||||||||||||||||||||||||||
Low risk | Moderate/High risk | ||||||||||||||||||||||||||||||||||||||
No further treatment Monitor with yearly fracture risk assessment with BMD testing every 2-3 years depending on risk factors | Age < 40 years 1. History of osteoporotic fracture, OR 2. Z score < -3 at hip or spine and prednisolone ≥ 7.5 mg/d, OR 3. >10%/year loss of BMD at hip or spine and prednisolone ≥ 7.5 mg/d, OR 4. Very high dose glucocorticoid and > 10 years | Age ≥ 40 years 1. History of osteoporotic fracture, OR 2. Men > 50 years and postmenopausal women with a BMD T-score ≤ -2.5, OR 3. FRAX 10-year risk for major osteoporotic fracture > 10%, OR 4. FRAX 10-year risk for hip osteoporotic fracture > 1%, OR 5. Very high dose of glucocorticoid | |||||||||||||||||||||||||||||||||||||
Treat with an oral bisphosphonate Second-line therapy: teriparatide Other suggested therapies (in order of preference) for high risk woman for whom the previous drugs are not appropriate: IV bisphosphonate Denosumab | Treat with an oral bisphosphonate Other suggested therapies (in order of preference): IV bisphosphonate Teriparatide Denosumab Raloxifen for postmenopausal women if no other therapy is available | ||||||||||||||||||||||||||||||||||||||
Effect of approved interventions for glucocorticoid-induced osteoporosis on BMD and fracture risk by National Osteoporosis Guideline Group (NOGG), UK, 2014[10]
Intervention | Spine BMD | Hip BMD | Vertebral fracture | Non-vertebral fracture |
---|---|---|---|---|
Alendronate | Highly effective | Highly effective | Moderately effective | Not adequately evaluated |
Etidronate | Highly effective | Highly effective | Highly effective | Not adequately evaluated |
Risedronate | Highly effective | Highly effective | Highly effective | Not adequately evaluated |
Zoledronic acid | Highly effective | Highly effective | Not adequately evaluated | Not adequately evaluated |
Teriparatide | Highly effective | Highly effective | Highly effective | Not adequately evaluated |
Bisphosphonates
Bisphosphonates are the first line treatment for osteoporosis disease. They are not indicated in people with severe renal function impairment; thus, it is important to check renal function and serum creatinine before prescription. These drugs need to be taken orally with large amount of water and not laying down until two hours following consumption, due to high risk of esophagitis. Rare but serious side effects may include osteonecrosis of the jaw and atypical femoral fractures.
- Alendronate: It is frequently used to treat osteoporosis in men, postmenopausal women, and also in corticosteroid-induced osteoporosis. Alendronate reduces the incidence of spine and hip fractures by about 50 % over 3 years in patients with a prior vertebral fracture or in patients who have osteoporosis at the hip site. It reduces the incidence of vertebral fractures by 48 % over 3 years in patients without a prior vertebral fracture.[6]
- The dosing is 70mg weekly per oral.
- Alendronate reduces hip, vertebral, and non-vertebral osteoporotic fractures.
- Risedronate: It is also used to treat Paget's disease. Risedronate decreases the bone mass loss. Also available in delayed release forms. Risendronate reduces the incidence of vertebral fractures by 41 to 49 % and nonvertebral fractures by 36 % over 3 years, with significant risk reduction occurring within 1 year of treatment in patients with a prior vertebral fracture.[15]
- The dosing is 35mg weekly or 150mg monthly per oral.
- Risedronate reduces vertebral fractures.
- Ibandronate: It is used to treat osteoporosis only in postmenopausal women. Ibandronate reduces the incidence of vertebral fractures by about 50 % over 3 years, but the reduction in risk of non-vertebral fracture with ibandronate has not been documented.[16]
- The dosing is 150mg monthly per oral, or 3mg every 3 months through intravenous (IV) route.
- Regarding that Ibandronate only reduced vertebral fractures and there is no evidence of non-vertebral fractures improvement, it is rarely prescribed.
- Zoledronic acid: It is also used for bone destruction due to Paget's disease, multiple myeloma, and metastatic bone tumors. Most potent bisphosphonate that has a higher risk of osteonecrosis of the jaw. Zoledronic acid reduces the incidence of vertebral fractures by 70% (with the significant reduction at 1 year), hip fractures by 41 %, and nonvertebral fractures by 25 % over 3 years in patients with osteoporosis defined by prevalent vertebral fractures and osteoporosis by BMD of the hip.[17]
- The dosing is 5mg annually through IV route.
- Zoledronate reduces hip, vertebral, and non-vertebral osteoporotic fractures. Common adverse effects are flu-like symptoms and bone pain, especially presented with the first dose.
National Osteoporosis Guideline Group (NOGG) algorithm for long term bisphosphonate therapy monitoring[10]
Abbreviations: FRAX: Fracture risk assessment tool[18]
Advise 3 years zoledronic acid or 5 years other bisphosphonates (follow up at 3/12 to discuss treatment issues) | |||||||||||||||||||||||||||||||||||||||
No fracture | |||||||||||||||||||||||||||||||||||||||
Recurrent fracture(s) Prevalent vertebral fracture(s) In patients taking oral bisphosphonate consider continuation if: • Age > 75 years • Previous hip fracture • Current oral glucocorticoid therapy ≥ 7.5 mg/d prednisolone | |||||||||||||||||||||||||||||||||||||||
FRAX+BMD after 3 years zoledronic acid or 5 years other bisphosphonates | |||||||||||||||||||||||||||||||||||||||
Above NOGG intervention threshold or Hip BMD T-score ≤ -2.5 | Below NOGG intervention threshold or Hip BMD T-score > -2.5 | ||||||||||||||||||||||||||||||||||||||
1. Check adherence 2. Exclude secondary cause 3. Re-evaluate treatment choice 4. Continue treatment | 1. Consider drug holiday 2. Repeat FRAX+BMD in 1.5-3 years | ||||||||||||||||||||||||||||||||||||||
Receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitor
- Denosumab: Human monoclonal antibody designed to inhibit RANKL (RANK ligand), a protein that acts as the primary signal for bone removal. It is used to treat osteoporosis in older men and postmenopausal women.
- The dosing is 60mg subcutaneous every 6 months.
- Denosumab reduces hip, vertebral, and non-vertebral osteoporotic fractures.
- The major side effects are eczema and nausea.[19]
- Romosozumab: Human monoclonal antibody designed to inhibit sclerostin, a blocking protein of canonical Wnt signaling bone formation pathway. It is used to prevent osteoporotic fractures in postmenopausal women.
- The dosing is 210mg subcutaneous monthly.
- Romosozumab reduces vertebral fractures.[20]
Selective estrogen receptor modulator (SERM)
- Raloxifene: it is the second line treatment of osteoporosis in postmenopausal women, for both treatment and prevention.
- The dosing is 60mg daily per oral. Raloxifene reduces vertebral fractures up to 35%.
- The major side effects are DVT and hot flashes in young pre-menopausal women.
- It has shown efficacy in reducing the prevalence and incidence of invasive breast cancer, too.[21]
- Teriparatide: The human recombinant parathyroid hormone used to treat the postmenopausal women with osteoporosis at high risk of fracture or to increase bone mass in men with osteoporosis.
- Usually, it is used in patients who cannot tolerate the oral bisphosphonates.
- It is also approved for corticosteroid induced osteoporosis.
- The dosing is 20mcg subcutaneous daily, approved for less than 2 years use.
- Teriparatide reduces vertebral and non-vertebral fractures, but not hip fracture.
- Common side effects include nausea, hypercalcemia, and hypercalciuria. However, patients with previous radiation therapy, paget's disease, or young patients should avoid this medication.
- Abaloparatide: The human recombinant parathyroid hormone used to treat the postmenopausal women with osteoporosis at high risk of fracture or to increase bone mass in men with osteoporosis.
- It has a shorter duration of action than teriparatide.
- The dosing is 80mcg subcutaneous daily, approved for less than 2 years use.
- Abaloparatide reduces vertebral and non-vertebral fractures.
- Common side effects are dizziness, headache, hypercalcemia, and hypercalciuria.[4]
Calcitonin
- Calcitonin is a hormone that inhibits the function of osteoclasts and resulting in growing bone mass. On the other hand, it can stimulate the osteoblast and also inhibit sclerostin production.
- It is used for postmenopausal women with osteoporosis.
- The dosing is 100units subcutaneous daily; or 200units intranasal daily.
- Calcitonin reduces vertebral fractures up to 30%. Common side effects are rhinitis, nausea, and flushing.[22]
Non-FDA-approved drugs for osteoporosis
Nonapproved agents include:
- Calcitriol: This synthetic vitamin D analog, which promotes calcium absorption, has been approved by the FDA for managing hypocalcemia and metabolic bone disease in renal dialysis patients. It is also approved for use in hypoparathyroidism, both surgical and idiopathic, and pseudohypoparathyroidism. No reliable data demonstrate a reduction of risk for osteoporotic fracture.
- Genistein: An isoflavone phytoestrogen which is the main ingredient in the prescription “medical food” product Fosteum® and generally regarded as safe by the FDA. Genistein may benefit bone health in postmenopausal women but more data are needed to fully understand its effects on bone health and fracture risk.
- Other bisphosphonates (etidronate, pamidronate, tiludronate): These medications vary chemically from alendronate, ibandronate, risedronate, and zoledronic acid but are in the same drug class. At this time, none is approved for prevention or treatment of osteoporosis. Most of these medications are currently approved for other conditions (e.g., Paget’s disease, hypercalcemia of malignancy, myositis ossificans).
- PTH (1-84): This medication is approved in some countries in Europe for treatment of osteoporosis in women. In one clinical study, PTH (1-84) effectively reduced the risk of vertebral fractures at a dose of 100 mcg/ day.
- Sodium fluoride: Through a process that is still unclear, sodium fluoride stimulates the formation of new bone. The quality of bone mass thus developed is uncertain, and the evidence that fluoride reduces fracture risk is conflicting and controversial.
- Strontium ranelate: This medication is approved for the treatment of osteoporosis in some countries in Europe. Strontium ranelate reduces the risk of both spine and nonvertebral fractures, but the mechanism is unclear. Incorporation of strontium into the crystal structure replacing calcium may be part of its mechanism of effect. These effects have only been documented with the pharmaceutical grade agent produced by Servier. This effect has not been studied in nutritional supplements containing strontium salts.
- Tibolone: Tibolone is a tissue-specific, estrogen-like agent that may prevent bone loss and reduce menopausal symptoms. It is indicated in Europe for the treatment of vasomotor symptoms of menopause and for prevention of osteoporosis, but it is not approved for use in the USA.[6]
References
- ↑ Papaioannou A, Santesso N, Morin SN, Feldman S, Adachi JD, Crilly R, Giangregorio LM, Jaglal S, Josse RG, Kaasalainen S, Katz P, Moser A, Pickard L, Weiler H, Whiting S, Skidmore CJ, Cheung AM (2015). "Recommendations for preventing fracture in long-term care". CMAJ. 187 (15): 1135–44, E450–61. doi:10.1503/cmaj.141331. PMC 4610837. PMID 26370055.
- ↑ Minisola S, Cipriani C, Occhiuto M, Pepe J (2017). "New anabolic therapies for osteoporosis". Intern Emerg Med. doi:10.1007/s11739-017-1719-4. PMID 28780668.
- ↑ Cummings SR, Karpf DB, Harris F, Genant HK, Ensrud K, LaCroix AZ, Black DM (2002). "Improvement in spine bone density and reduction in risk of vertebral fractures during treatment with antiresorptive drugs". Am. J. Med. 112 (4): 281–9. PMID 11893367.
- ↑ 4.0 4.1 4.2 Ensrud KE, Crandall CJ (2017). "Osteoporosis". Ann. Intern. Med. 167 (3): ITC17–ITC32. doi:10.7326/AITC201708010. PMID 28761958.
- ↑ Bauer DC (2013). "Clinical practice. Calcium supplements and fracture prevention". N. Engl. J. Med. 369 (16): 1537–43. doi:10.1056/NEJMcp1210380. PMC 4038300. PMID 24131178.
- ↑ 6.0 6.1 6.2 Cosman, F.; de Beur, S. J.; LeBoff, M. S.; Lewiecki, E. M.; Tanner, B.; Randall, S.; Lindsay, R. (2014). "Clinician's Guide to Prevention and Treatment of Osteoporosis". Osteoporosis International. 25 (10): 2359–2381. doi:10.1007/s00198-014-2794-2. ISSN 0937-941X.
- ↑ "Juvenile Osteoporosis".
- ↑ Händel MN, Cardoso I, von Bülow C, Rohde JF, Ussing A, Nielsen SM; et al. (2023). "Fracture risk reduction and safety by osteoporosis treatment compared with placebo or active comparator in postmenopausal women: systematic review, network meta-analysis, and meta-regression analysis of randomised clinical trials". BMJ. 381: e068033. doi:10.1136/bmj-2021-068033. PMC 10152340 Check
|pmc=
value (help). PMID 37130601 Check|pmid=
value (help). - ↑ Qaseem A, Hicks LA, Etxeandia-Ikobaltzeta I, Shamliyan T, Cooney TG, Clinical Guidelines Committee of the American College of Physicians; et al. (2023). "Pharmacologic Treatment of Primary Osteoporosis or Low Bone Mass to Prevent Fractures in Adults: A Living Clinical Guideline From the American College of Physicians". Ann Intern Med. 176 (2): 224–238. doi:10.7326/M22-1034. PMID 36592456 Check
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value (help). - ↑ 10.0 10.1 10.2 Cosman F, de Beur SJ, LeBoff MS, Lewiecki EM, Tanner B, Randall S; et al. (2014). "Clinician's Guide to Prevention and Treatment of Osteoporosis". Osteoporos Int. 25 (10): 2359–81. doi:10.1007/s00198-014-2794-2. PMC 4176573. PMID 25182228.
- ↑ Janz, Kathleen F.; Letuchy, Elena M.; Francis, Shelby L.; Metcalf, Kristen M.; Burns, Trudy L.; Levy, Steven M. (2014). "Objectively Measured Physical Activity Predicts Hip and Spine Bone Mineral Content in Children and Adolescents Ages 5â€"15 Years: Iowa Bone Development Study". Frontiers in Endocrinology. 5. doi:10.3389/fendo.2014.00112. ISSN 1664-2392.
- ↑ Griffin LM, Thayu M, Baldassano RN, DeBoer MD, Zemel BS, Denburg MR, Denson LA, Shults J, Herskovitz R, Long J, Leonard MB (2015). "Improvements in Bone Density and Structure during Anti-TNF-α Therapy in Pediatric Crohn's Disease". J. Clin. Endocrinol. Metab. 100 (7): 2630–9. doi:10.1210/jc.2014-4152. PMC 4490303. PMID 25919459.
- ↑ Rauch F, Glorieux FH (2005). "Bisphosphonate treatment in osteogenesis imperfecta: which drug, for whom, for how long?". Ann. Med. 37 (4): 295–302. doi:10.1080/07853890510007386. PMID 16019729.
- ↑ Buckley, Lenore; Guyatt, Gordon; Fink, Howard A.; Cannon, Michael; Grossman, Jennifer; Hansen, Karen E.; Humphrey, Mary Beth; Lane, Nancy E.; Magrey, Marina; Miller, Marc; Morrison, Lake; Rao, Madhumathi; Robinson, Angela Byun; Saha, Sumona; Wolver, Susan; Bannuru, Raveendhara R.; Vaysbrot, Elizaveta; Osani, Mikala; Turgunbaev, Marat; Miller, Amy S.; McAlindon, Timothy (2017). "2017 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis". Arthritis & Rheumatology. 69 (8): 1521–1537. doi:10.1002/art.40137. ISSN 2326-5191.
- ↑ Harris ST, Watts NB, Genant HK, McKeever CD, Hangartner T, Keller M, Chesnut CH, Brown J, Eriksen EF, Hoseyni MS, Axelrod DW, Miller PD (1999). "Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. Vertebral Efficacy With Risedronate Therapy (VERT) Study Group". JAMA. 282 (14): 1344–52. PMID 10527181.
- ↑ Chesnut CH, Skag A, Christiansen C, Recker R, Stakkestad JA, Hoiseth A, Felsenberg D, Huss H, Gilbride J, Schimmer RC, Delmas PD (2004). "Effects of oral ibandronate administered daily or intermittently on fracture risk in postmenopausal osteoporosis". J. Bone Miner. Res. 19 (8): 1241–9. doi:10.1359/JBMR.040325. PMID 15231010.
- ↑ Black DM, Delmas PD, Eastell R, Reid IR, Boonen S, Cauley JA, Cosman F, Lakatos P, Leung PC, Man Z, Mautalen C, Mesenbrink P, Hu H, Caminis J, Tong K, Rosario-Jansen T, Krasnow J, Hue TF, Sellmeyer D, Eriksen EF, Cummings SR (2007). "Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis". N. Engl. J. Med. 356 (18): 1809–22. doi:10.1056/NEJMoa067312. PMID 17476007.
- ↑ "www.sheffield.ac.uk".
- ↑ McClung MR, Lewiecki EM, Geller ML, Bolognese MA, Peacock M, Weinstein RL, Ding B, Rockabrand E, Wagman RB, Miller PD (2013). "Effect of denosumab on bone mineral density and biochemical markers of bone turnover: 8-year results of a phase 2 clinical trial". Osteoporos Int. 24 (1): 227–35. doi:10.1007/s00198-012-2052-4. PMC 3536967. PMID 22776860.
- ↑ Bandeira L, Lewiecki EM, Bilezikian JP (2017). "Romosozumab for the treatment of osteoporosis". Expert Opin Biol Ther. 17 (2): 255–263. doi:10.1080/14712598.2017.1280455. PMID 28064540.
- ↑ Lippuner K, Buchard PA, De Geyter C, Imthurn B, Lamy O, Litschgi M, Luzuy F, Schiessl K, Stute P, Birkhäuser M (2012). "Recommendations for raloxifene use in daily clinical practice in the Swiss setting". Eur Spine J. 21 (12): 2407–17. doi:10.1007/s00586-012-2404-y. PMC 3508239. PMID 22739699.
- ↑ Felsenfeld, A. J.; Levine, B. S. (2015). "Calcitonin, the forgotten hormone: does it deserve to be forgotten?". Clinical Kidney Journal. 8 (2): 180–187. doi:10.1093/ckj/sfv011. ISSN 2048-8505.