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The mainstays of treatment in primary [[osteoporosis]] [[disease]] are based on in life style modifications. Most of the time in high risk patients and people with past history of [[Osteoporosis|osteoporotic]] [[fracture]], [[Medical therapy template|medical therapy]] is necessary. [[Bisphosphonates]] are the '''''first line''''' treatment for [[osteoporosis]] [[disease]]. [[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 elder men and [[postmenopausal]] women. [[Teriparatide]] and Abaloparatide are human [[recombinant]] [[parathyroid hormone]]<nowiki/>s used to treat [[postmenopausal]] woman with [[osteoporosis]] at high risk of [[fracture]] or to increase [[bone]] mass in men with [[osteoporosis]]. | The mainstays of treatment in primary [[osteoporosis]] [[disease]] are based on in life style modifications. Most of the time in high risk patients and people with past history of [[Osteoporosis|osteoporotic]] [[fracture]], [[Medical therapy template|medical therapy]] is necessary. [[Bisphosphonates]] are the '''''first line''''' treatment for [[osteoporosis]] [[disease]]. [[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 elder men and [[postmenopausal]] women. [[Teriparatide]] and Abaloparatide are human [[recombinant]] [[parathyroid hormone]]<nowiki/>s used to treat [[postmenopausal]] woman with [[osteoporosis]] at high risk of [[fracture]] or to increase [[bone]] mass in men with [[osteoporosis]]. | ||
== | ==Medical therapy== | ||
* Most of the time in high risk patients and people with past history of [[Osteoporosis|osteoporotic]] [[fracture]], [[Medical therapy template|medical therapy]] is necessary.<ref name="pmid28780668">{{cite journal| author=Minisola S, Cipriani C, Occhiuto M, Pepe J| title=New anabolic therapies for osteoporosis. | journal=Intern Emerg Med | year= 2017 | volume= | issue= | pages= | pmid=28780668 | doi=10.1007/s11739-017-1719-4 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28780668 }}</ref> | * Most of the time in high risk patients and people with past history of [[Osteoporosis|osteoporotic]] [[fracture]], [[Medical therapy template|medical therapy]] is necessary.<ref name="pmid28780668">{{cite journal| author=Minisola S, Cipriani C, Occhiuto M, Pepe J| title=New anabolic therapies for osteoporosis. | journal=Intern Emerg Med | year= 2017 | volume= | issue= | pages= | pmid=28780668 | doi=10.1007/s11739-017-1719-4 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28780668 }}</ref> | ||
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=== Medical therapy candidates === | === Medical therapy candidates === | ||
* The national [[osteoporosis]] foundation (NOF) declare that [[osteoporosis]] treatment has to prescribed for followings: | * The national [[osteoporosis]] foundation (NOF) declare that [[osteoporosis]] treatment has to prescribed for followings: | ||
* | ** 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 -1.0 > T-score > -2.5 SD with high risk of [[Osteoporosis|osteoporotic]] [[Bone fracture|fracture]] | ||
* | ** Men with [[hypogonadism]] that [[testosterone]] therapy is contraindicated<ref name="pmid28761958" /> | ||
=== Medical therapy options === | === Medical therapy options === | ||
'''1 Stage 1 - Osteoporosis''' | |||
* 1.1 '''Increasing bone mineral density (BMD)''' | |||
** 1.1.1 '''Adult''' | |||
*** Preferred regimen (1): Alendronate 70 mg PO weekly '''(Contraindications/specific instructions)''' | |||
*** 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): Raloxifen 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 (3): Calcitonin 100 units SC daily OR 200 units intranasal daily | |||
==== '''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 have to taken [[Orally ingested|orally]] with large amount of water, 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]]. | [[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 have to taken [[Orally ingested|orally]] with large amount of water, 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''']]: | * [[Alendronate|'''Alendronate''']]: It is frequently used to treat [[osteoporosis]] in men, [[postmenopausal]] women, and also in [[corticosteroid]]-induced [[osteoporosis]]. | ||
** 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''']]: | * [[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. | ||
** 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''']]: | * [[Ibandronate|'''Ibandronate''']]: It is used to treat osteoporosis only in [[postmenopausal]] women. | ||
** The dosing is 150mg monthly per oral; or 3mg every 3 months through [[Intravenous|intravenous (IV)]] rout. | ** The dosing is 150mg monthly per oral; or 3mg every 3 months through [[Intravenous|intravenous (IV)]] rout. | ||
** 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''']]: | * [[Zoledronic acid|'''Zoledronic''' '''acid''']]: It is also used for [[bone]] destructions due to [[Paget's disease]], [[multiple myeloma]], and [[metastatic]] [[bone tumors]]. Most potent [[bisphosphonate]] that has a higher risk of [[osteonecrosis of the jaw]]. | ||
** 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 first dose. | ||
==== Receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitor ==== | ==== Receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitor ==== | ||
* '''[[Denosumab]]:''' | * '''[[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 elder 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''': | *'''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. | ||
**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]]''': Human [[recombinant]] [[parathyroid hormone]] used to treat [[postmenopausal]] woman 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]]. | ||
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**[[Teriparatide]] reduces [[vertebral]] and non-[[vertebral]] [[fractures]], but not reduced [[hip fracture]]. | **[[Teriparatide]] reduces [[vertebral]] and non-[[vertebral]] [[fractures]], but not reduced [[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''': Human [[recombinant]] [[parathyroid hormone]] used to treat [[postmenopausal]] woman 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. | ||
Revision as of 03:57, 15 August 2017
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Cafer Zorkun, M.D., Ph.D. [2], Raviteja Guddeti, M.B.B.S.[3]
Overview
The mainstays of treatment in primary osteoporosis disease are based on in 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 disease. 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 elder men and postmenopausal women. Teriparatide and Abaloparatide are human recombinant parathyroid hormones used to treat postmenopausal woman with osteoporosis at high risk of fracture or to increase bone mass in men with osteoporosis.
Medical therapy
- Most of the time in high risk patients and people with past history of osteoporotic fracture, medical therapy is necessary.[1]
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 are measured by the extend they improve the fracture risk, in turn of increasing BMD.[2]
- It has to explain for patients that treatment purpose is to reduce their fracture risk in the future. During the treatment, if a single fracture happened, it is not necessarily reflect of treatment failure; despite the major complicates fractures that may need to start alternative treatments or patient referral to specialist.[3]
- 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 has various dosage forms.[4]
Medical therapy candidates
- The national osteoporosis foundation (NOF) declare that osteoporosis treatment has to prescribed for followings:
- 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 that testosterone therapy is contraindicated[3]
Medical therapy options
1 Stage 1 - Osteoporosis
- 1.1 Increasing bone mineral density (BMD)
- 1.1.1 Adult
- Preferred regimen (1): Alendronate 70 mg PO weekly (Contraindications/specific instructions)
- 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): Raloxifen 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 (3): Calcitonin 100 units SC daily OR 200 units intranasal daily
- 1.1.1 Adult
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 have to taken orally with large amount of water, 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.
- 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.
- 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.
- The dosing is 150mg monthly per oral; or 3mg every 3 months through intravenous (IV) rout.
- 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 destructions due to Paget's disease, multiple myeloma, and metastatic bone tumors. Most potent bisphosphonate that has a higher risk of osteonecrosis of the jaw.
- 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 first dose.
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 elder men and postmenopausal women.
- Romosozumab: Human monoclonal antibody designed to sclerostin, 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.[6]
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.[7]
- Teriparatide: Human recombinant parathyroid hormone used to treat postmenopausal woman 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 reduced 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: Human recombinant parathyroid hormone used to treat postmenopausal woman 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.[3]
Calcitonin
- Calcitonin is a hormone that inhibit the function of osteoclasts and result 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.[8]
References
- ↑ 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.
- ↑ 3.0 3.1 3.2 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.
- ↑ 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.