Osteoporosis resident survival guide

For Osteoporosis click here.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Eiman Ghaffarpasand, M.D. [2]

Osteoporosis Resident Survival Guide Microchapters
Overview
Classification
Causes
FIRE
Diagnosis
Treatment
Do's
Don'ts

Overview

Osteoporosis was first discovered by John Hunter, British surgeon, in 1800's. Osteoporosis divided to primary and secondary diseases, upon classification based on disease origin. While, it becomes divided to osteopenia, osteoporosis, and severe osteoporosis, upon classification based on disease severity. The pathophysiology of osteoporosis basically involves an imbalance between bone resorption and bone formation. Major factors that contribute to the development of osteoporosis include estrogen deficit and aging. The main pathway, through which these factors might lead to osteoporosis is reactive oxygen species (ROS) damage to osteocytes. Decreasing the capability of autophagy in osteocytes is another important issue; which make them vulnerable to oxidative stresses. Genes involved in the pathogenesis of osteoporosis are many genes that majorly can categorized in four main groups, include the osteoblast regulatory genes, osteoclast regulatory genes, bone matrix elements genes, and hormone/receptor genes. Osteoporosis must be differentiated from other diseases that cause decreasing in bone mineral density (BMD), such as idiopathic transient osteoporosis of hip, osteomalacia, scurvy, osteogenesis imperfecta, multiple myeloma, homocystinuria, and hypermetabolic resorptive osteoporosis. Osteoporosis is a major health problem involving 43.9% (43.4 million) of male and female population in the United States. White females and African-American males have the highest frequency among the other races. Risk factors for osteoporosis disease are of two types, including non-modifiable and modifiable (potentially) factors. Non-modifiable risk factors are age, sex, menopause, and family history. Modifiable (potentially) factors are smoking, alcohol consumption, immobility, glucocorticoid abuse, and proton pump inhibitor (PPI). Today, risk of fracture due to osteoporosis is threatening one out of two postmenopausal women and also one out of five older men. The 10-year risk for any osteoporosis-related fractures in 65-year-old white woman with no other risk factor is 9.3%. Upon the guidelines of USPSTF, all women ≥ 65 years old along with women < 65 years old with high risk of fracture are target of screening for osteoporosis; but there is not any recommendation to screen men for the disease. There are two major methods, that is suggested to use for screening osteoporosis, include dual energy x-ray absorptiometry (DXA) of both hip and lumbar spine bones, and quantitative ultrasonography of the calcaneus. If left untreated, most of patients with osteoporosis may progress to develop fracture. With appropriate and timely usage of medications along with calcium and/or vitamin D supplementation, the outcome of osteoporosis is usually good. The mainstays of treatment in primary osteoporosis disease are based on in lifestyle 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.

Classification

Osteoporosis may be classified into several subtypes based on disease origin, and disease severity.

Osteoporosis classifications

Based on Disease severity

Based on Disease etiology

T-score measurement

Bone loss due to other diseases?

-1>T-score>-2.5

T-score≤-2.5

T-score≤-2.5 plus history of fracture

No

Yes

Osteopenia

Osteoporosis

Severe osteoporosis

Primary osteoporosis

Secondary osteoporosis

Juvenile Osteoporosis (JO)

Osteoporosis in children and adolescents is rare, usually is due to some comorbidities or medications, secondary osteoporosis. Surprisingly, no significant causes have been found for rare cases, idiopathic osteoporosis.

No matter what causes it, juvenile osteoporosis can be a significant problem because it occurs during the child’s prime bone-building years. From birth through young adulthood, children steadily accumulate bone mass, which peaks sometime before age 30. The greater their peak bone mass, the lower their risk for osteoporosis later in life. After people reach their mid thirties, bone mass typically begins to decline—very slowly at first but increasing in their fifties and sixties. Both heredity and lifestyle choices—especially the amount of calcium in the diet and the level of physical activity influence the development of peak bone mass and the rate at which bone is lost later in life.

Secondary Osteoporosis

• As the primary condition, juvenile idiopathic arthritis (also known as juvenile rheumatoid arthritis) provides a good illustration of the possible causes of secondary osteoporosis. In some cases, the disease process itself can cause osteoporosis.
• In other cases, medication used to treat the primary disorder may reduce bone mass. For example, drugs such as prednisone, used to treat severe cases of juvenile idiopathic arthritis, negatively affect bone mass.
• Finally, some behaviors associated with the primary disorder may lead to bone loss or reduction in bone formation. For example, a child with juvenile idiopathic arthritis may avoid physical activity, which is necessary for building and maintaining bone mass, because it may aggravate his or her condition or cause pain.

Idiopathic Juvenile Osteoporosis

• Idiopathic juvenile osteoporosis (IJO) is a primary condition with no known cause. It is diagnosed after other causes of juvenile osteoporosis have been excluded. This rare form of osteoporosis typically occurs just before the onset of puberty in previously healthy children. The average age at onset is 7 years, with a range of 1 to 13 years. Most children experience complete recovery of bone.

• The first sign of IJO is usually pain in the lower back, hips, and feet, often accompanied by difficulty walking. Knee and ankle pain and fractures of the lower extremities also may occur. Physical malformations include kyphosis, loss of height, a sunken chest, or a limp. These physical malformations are sometimes reversible after IJO has run its course.

• X-rays of children with IJO often show low bone density, fractures of weight-bearing bones, and collapsed or misshapen vertebrae. However, conventional X-rays may not be able to detect osteoporosis until significant bone mass already has been lost. Newer methods such as dual energy x-ray absorptiometry (DXA), and quantitative computed tomography (QCT ) allow for earlier and more accurate diagnosis of low bone mass.

• There is no established medical or surgical therapy for juvenile osteoporosis. In some cases, no treatment may be needed because the condition usually goes away 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, some medications called bisphosphonates, approved by the Food and Drug Administration for the treatment of osteoporosis in adults, have been given to children experimentally.
• Most children with IJO experience a complete recovery of bone tissue. Although growth may be somewhat impaired during the acute phase of the disorder, normal growth resumes—and catch-up growth often occurs—afterward. Unfortunately, in some cases, IJO can result in permanent disability such as kyphoscoliosis or collapse of the rib cage.

Causes

Life Threatening Causes

Life-threatening causes include conditions which may result in death or permanent disability within 24 hours if left untreated. There are no life-threatening causes of osteoporosis, however complications resulting from untreated osteoporosis are common.

Common and Less Common Causes

Osteoporosis causes

Non-modifiable

Modifiable

Physiologic

Musculoskeletal genetic disorder

Progeria genetic disorder

Life style

Hormonal disorder

Medication

Medical condition

•Aging •Idiopathic •Menopause •Andropause •Excessive Dieting

•Abderhalden-Kaufmann-Lignac syndrome •Acromegaly •Acroosteolysis neurogenic •Albright's hereditary osteodystrophy •Alpha thalassemia •Boyd-Stearns syndrome •Chromosome 1, deletion q21 q25 •Cystathionine beta-synthase deficiency •Diamond-Blackfan anemia •Dibasic aminoaciduria 2 •Dyskeratosis Congenital •Eccentrochondrodysplasia •Fabry's disease •Fanconi-Albertini-Zellweger syndrome •Glycerol kinase deficiency •Gnathodiaphyseal dysplasia •Hajdu-Cheney syndrome •Homocystinuria •Hyperostosis corticalis deformans juvenilis •Hypertrichotic osteochondrodysplasia •Iridogoniodysgenesis and skeletal anomalies •Kaler-Garrity-Stern syndrome •Larsen syndrome, recessive type •Lobstein disease •Lysinuric protein intolerance •Marie-Bamberg syndrome •Menkes Disease •Metaphyseal chondrodysplasia Spahr type •Metaphyseal dysplasia Pyle type •Morquio syndrome •Nodulosis-arthropathy-osteolysis syndrome •Osteochondrodysplatic dwarfism -- deafness -- retinitis pigmentosa •Osteogenesis imperfecta •Osteoporosis -- macrocephaly -- mental retardation -- blindness

•Mixed connective tissue disease •Paget's disease of bone •Osteoporosis -- oculocutaneous -- hypopigmentation syndrome •Osteoporosis-pseudoglioma syndrome •Pelizaeus-Merzbacher disease, recessive, acute infantile •Pena Shokeir syndrome •Peroxisomal bifunctional enzyme deficiency •Pointer syndrome •Prader-Willi syndrome •Prolidase deficiency •Otospondylomegaepiphyseal dysplasia •Reflex sympathetic dystrophy syndrome •Sakati syndrome •Schwartz-Jampel Syndrome •Shprintzen-Golberg craniosynostosis •Singleton-Merten syndrome •Snyder-Robinson syndrome •Spinocerebellar ataxia -- dysmorphism •Sponastrime dysplasia •Spondyloepimetaphyseal dysplasia with multiple dislocations •Spondylometaphyseal dysplasia with dentinogenesis imperfecta •Spondylo-ocular syndrome •Thick skull syndrome •Torg osteolysis syndrome •Tricho-hepato-enteric syndrome •Systemic infantile hyalinosis •Urban rogers meyer syndrome •Waldenstrom's macroglobulinemia •Winchester syndrome •Wolcott-Rallison syndrome •Xylosylprotein 4-beta-galactosyltransferase (XGPT) deficiency

•Ehlers-Danlos syndrome- progeroid form •Fanconi-ichthyosis-dysmorphism •Geroderma osteodysplastica •Hutchinson Gilford Syndrome •Hyperglycerolemia - infantile form •Infantile sialic acid storage disorder •Premature aging •Pseudoprogeria syndrome •Storm syndrome •Werner syndrome

•Alcoholism •Calcium deficiency •Immobility •Copper deficiency •Female athlete triad •Protein deficiency •Underweight •White Phosphorus poisoning •Zero gravity

•Gonadal dysgenesis •Hyperparathyroidism •Hyperthyroidism •Hypophosphatemic rickets •Primary hypoparathyroidism •Adrenal adenoma •Adrenal incidentaloma •Adrenocortical carcinoma •Aromatase deficiency •Cushing's disease •Cushing's syndrome •Functioning pancreatic endocrine tumor •Galactorrhea-Hyperprolactinaemia •Hashimoto's Thyroiditis •Hyperadrenalism •Hypogonadotropic hypogonadism -- Syndactyly •Hyperprolactinemia •Kallmann syndrome •Klinefelter syndrome •Lactotroph adenoma •Oophorectomy - bilateral •Orchidectomy •Ovarian insufficiency due to FSH resistance •Ovarian insufficiency, familial •Primary hypoparathyroidism •Sub clinical hypothyroidism •Turner's syndrome •Wolman syndrome

•Prednisolone •Cyproterone •Ethanol •Exemestane •Flunisolide •Fluticasone (aerosol) •Heparin •Isotretinoin •Pergolide

•Chronic renal failure •Ankylosing spondylitis •Brown-Sequard Syndrome •Chronic acidosis •Chronic Hepatitis •Chronic Liver Disease •Chronic obstructive pulmonary disease •Crohn's disease •Cystic Fibrosis •Depression •Generalized mastocytosis •Haemochromatosis •Hemoglobin H disease •Hyper IgE syndrome / Job syndrome •Leukemia •Lymphoma •Maldigestion •Oncogenic osteomalacia •Pregnancy •Postgastrectomy •Primary biliary cirrhosis •Renal osteodystrophy •Sarcoidosis •Sickle cell anemia •Tuberous sclerosis •Ulcerative colitis •Wilson's Disease

FIRE: Focused Initial Rapid Evaluation

Lifestyle modifications

Exercise

Calcium Supplementation

Vitamin D supplementation

Smoking cessation

Reduced alcohol consumption

Hip protectors

Fall protection

• Balance, strength and functional training exercises

Women • 9-18 yrs: 1,300 mg • 19-50 yrs: 1,000 mg • 51-70 yrs: 1,200 mg • 71 and more yrs: 1,200 mg Men • 50-70 yrs: 1,000 mg • 71 and more yrs: 1,200 mg

Women • 9-18 yrs: 600 IU • 19-50 yrs: 600 IU • 51-70 yrs: 600 IU • 71 and more yrs: 800 IU Men • More than 50 yrs: 800-1,000 IU • Serum vitamin D level of 20 ng per mL (50 nmol per L) is recommended for good bone health

• Stop-smoking program and nicotine patch

Limit to: • One drink/day for women • Two drinks/day for men • Moderate alcohol may associated with slightly higher BMD and lower fracture risk in postmenopausal women

• Hard and soft hip protectors, upon preference

Multifactorial interventions: • Individual risk assessment • Tai Chi and other exercise programs • Home safety assessment and modification by an occupational therapist • Gradual withdrawal of psychotropic medication • Visual impairment correction • Improve mobility

Chronic glucocorticoid (GC) use

Children and adolescent

Adults

Children

< 40 yrs

≥ 40 yrs

Men

Women

Clinical fracture risk assessment*: • Within 6 months of the start of GC treatment • Every 12 months during GC treatment • No need to BMD measurement

As soon as possible but at least within 6 months of the initiation of GC treatment if: • High fracture risk • Significant osteoporotic risk factors (malnutrition, significant weight loss or low body weight, hypogonadism, secondary hyperparathyroidism, thyroid disease, family history of hip fracture, smoking, alcohol use) Every 2-3 yrs of GC treatment if: • Moderate-to-high fracture risk •• History of previous fracture •• BMD Z score <-3 •• Received very high-dose prednisone [≥30 mg/day and cumulative dose >5 gm] •• Risks for poor medication adherence or absorption •• Multiple osteoporotic risk factors

≥ 40 yrs

• 18 yrs of age or 2 yrs after chemotherapy • Severe diseases • Low body weight • Chronic corticosteroid use • Delayed puberty • Gonadal failure • History of low-impact fracture

• Young hypogonadal • More than 70 yrs • Less than 70 yrs with: ••Low body weight ••Prior fracture ••High risk medication use ••Disease or condition associated with bone loss

• More than 65 yrs • Postmenopausal women younger than 65 yrs with: ••History of fragility fracture •• Weigh less than 127 lb (58 kg) ••Medications or diseases that cause bone loss •• Parental history of hip fracture •• smoking •• Alcoholism •• Rheumatoid arthritis.

Diagnosis

Treatment

Do's

Dont's

References