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Osteoporosis
David A. Ross, MD
Rahul Kapur, MD, CAQSM
image BASICS
DESCRIPTION
A skeletal disease characterized by low bone mass, deterioration of bone tissue, and disruption of bone architecture that leads to compromised bone strength and an increased risk of fracture.
EPIDEMIOLOGY
  • Most common bone disease in humans
  • Predominant age: elderly >60 years of age
  • Predominant sex: female > male (80%/20%)
Incidence
Of persons age >50 years, 9% had osteoporosis at either the femoral neck or lumbar spine.
Prevalence
  • >9.9 million Americans have osteoporosis.
  • Women >50 years of age: 24%
  • Men >50 years of age: 7.5%
  • 50% of postmenopausal women will have an osteoporotic fracture during their lifetime and 15% will experience a hip fracture.
  • Two million fractures are attributed to osteoporosis on an annual basis in the United States.
ETIOLOGY AND PATHOPHYSIOLOGY
  • Imbalance between bone resorption and bone formation
  • Aging
  • Hypoestrogenemia
Genetics
  • Familial predisposition
  • More common in Caucasians and Asians than in African Americans and Hispanics
RISK FACTORS
  • Nonmodifiable
    • Advanced age (>65 years)
    • Female gender and menopause
    • Caucasian or Asian
    • Family history of osteoporosis
    • History of atraumatic fracture
  • Modifiable
    • Low body weight (58 kg or body mass index [BMI] <21)
    • Calcium/vitamin D deficiency
    • Inadequate physical activity
    • Cigarette smoking
    • Excessive alcohol intake (>3 drinks/day)
    • Medications: see “Commonly Associated Conditions”
GENERAL PREVENTION
The aim in the prevention and treatment of osteoporosis is to prevent fracture:
  • Regularly perform weight-bearing exercise.
  • Consume a diet that includes adequate calcium (1,000 mg/day for men aged 50 to 70; 1,200 mg/day for women aged 51 + years and men 70 + years) and vitamin D (800 to 1,000 IU/day).
  • The USPSTF has concluded that vitamin D supplementation is effective in preventing falls in community-dwelling adults aged ≥65 years who are at increased risk for falls (1)[B].
  • Evidence is insufficient to assess the balance of the benefits and harms of daily supplementation with >400 IU of vitamin D3 and >1,000 mg of calcium for the primary prevention of fractures in noninstitutionalized postmenopausal women (1)[B].
  • USPSTF recommends against daily supplementation with <400 IU of vitamin D3 and <1,000 of calcium for the primary prevention of fractures in noninstitutionalized postmenopausal women (1)[B].
  • Avoid smoking.
  • Limit alcohol consumption (<3 drinks/day).
  • Fall prevention (vitamin D supplementation, home safety assessment, correction of visual impairment)
  • Screen (USPSTF recommendations):
    • All women ≥65 years of age (1)[B]
    • Women >50 years of age with ≥10-year fracture risk (using the WHO's Fracture Risk Assessment [FRAX] Tool) >9.3%
    • The current evidence is insufficient to assess the balance of benefits and harms of screening for osteoporosis in men; however, The National Osteoporosis Foundation recommends screening men age >70 years, especially if at increased risk.
COMMONLY ASSOCIATED CONDITIONS
  • Malabsorption syndromes: gastrectomy, inflammatory bowel disease, celiac disease
  • Hypoestrogenism: menopause, hypogonadism, eating disorders, female athlete triad
  • Endocrinopathies: hyperparathyroidism, hyperthyroidism, hypercortisolism, diabetes mellitus
  • Hematologic disorders: hemophilia, sickle cell disease, multiple myeloma, thalassemia, hemochromatosis
  • Other disorders: multiple sclerosis, end stage renal disease, rheumatoid arthritis, lupus, chronic obstructive pulmonary disease (COPD), HIV/AIDS
  • Medications: antiepileptics, aromatase inhibitors (raloxifene), chronic corticosteroids (>5 mg prednisone or equivalent for >3 months), medroxyprogesterone acetate, heparin, SSRI, thyroid hormone (in supraphysiologic doses), proton pump inhibitors
image DIAGNOSIS
PHYSICAL EXAM
  • Thoracic kyphosis, poor balance, deconditioning
  • Historical height loss >1.5 cm (difference between current height and peak height at age 20)
  • Prospective height loss >2 cm (difference between current height and previously documented height)
DIFFERENTIAL DIAGNOSIS
  • Multiple myeloma/other neoplasms
  • Osteomalacia
  • Type I collagen mutations
  • Osteogenesis imperfecta
DIAGNOSTIC TESTS & INTERPRETATION
Dual-energy x-ray absorptiometry (DEXA) of the lumbar spine/hip is considered the gold standard for the diagnosis of osteoporosis.
Initial Tests (lab, imaging)
Consider in screening for secondary osteoporosis:
  • Serum 25-hydroxyvitamin D and parathyroid hormone
  • CBC
  • Serum chemistry, including calcium, phosphorus, magnesium, total protein, albumin, liver enzymes, creatinine, alkaline phosphatase, and thyroid stimulating hormone
  • Urinalysis (24-hour collection) for calcium, sodium, and creatinine (to identify calcium malabsorption of hypercalciuria)
  • DEXA of the lumbar spine/hip is the gold standard for measuring bone mineral density (BMD).
  • A BMD at the hip or lumbar spine that is ≤2.5 standard deviations (SDs) below the mean BMD of a young-adult reference population is diagnostic of osteoporosis.
  • A minimum of 2 years may be needed to reliably measure a change in BMD.
  • BMD is expressed in terms of T-scores and Z-scores:
    • T-score is the number of SDs a patient's BMD deviates from the mean for young, normal (age 25 to 40 years) control individuals of the same sex.
    • WHO defines normal BMD as a T-score ≥-1, osteopenia as a T-score between - 1 and - 2.5, and osteoporosis as a T-score ≤-2.5.
    • WHO thresholds can be used for postmenopausal women and men >50 years of age.
    • The Z-score is a comparison of the patient's BMD with an age-matched population.
    • A Z-score <-2 should prompt evaluation for causes of secondary osteoporosis.
  • Quantitative ultrasound densitometry does not measure BMD directly but may be used clinically in predicting fractures in postmenopausal women and in men >65 (2).
  • Plain radiographs lack sensitivity to diagnose osteoporosis, but an abnormality (e.g., widened intervertebral spaces, rib fractures, vertebral compression fractures) should prompt evaluation.
Follow-Up Tests & Special Considerations
Further labs depending on initial evaluation, Z-score -2.5 or lower or young age
  • Iron and ferritin (hemochromatosis)
  • Testosterone levels (hypogonadism in men)
  • Serum protein electrophoresis and free &kgr; and &lgr; light chains (multiple myeloma)
  • Urinary-free cortisol (Cushing disease)
  • Tissue transglutaminase antibodies (celiac disease)
  • Markers of bone resorption (urine N-telopeptides of type 1 collagen, serum C-telopeptides of type 1 collagen, serum N-terminal propeptide of type 1 procollagen): no prospective studies supporting use in osteoporosis diagnosis and management; potential role for identifying patients at high risk for fracture and monitoring response to therapy
Diagnostic Procedures/Other
Bone biopsy may be recommended for patients with bone disease and renal failure to establish the correct diagnosis as it can assess the degree of mineralization and microarchitecture and specific bone loss mechanisms.
Test Interpretation
  • In osteoporosis can see reduced skeletal mass; trabecular bone thinned or lost more than cortical bone
  • Can assess osteoclast and osteoblast relative activity
  • Can rule out other metabolic bone diseases
  • Can assess if bone marrow is normal or atrophic
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image TREATMENT
  • All patients with a T-score ≤-2.5 with no risk factors
  • All postmenopausal women who have had an osteoporotic vertebral/hip fracture
  • All postmenopausal women who have BMD values consistent with osteoporosis (T-score ≤2.5) at the lumbar spine, femoral neck, or total hip region
  • Postmenopausal women with T-scores from -1.0 to -2.5 and a 10-year risk, based on FRAX calculator, of an osteoporotic fracture (spine, hip, shoulder, and wrist) of at least 20% or hip of at least 3%
  • Treat men >50 years of age who present with a hip or vertebral fracture or a T-score <-2.5 after appropriate evaluation; however, evidence for the effectiveness of treatment of osteoporosis in men is limited.
MEDICATION
Calcium 1,200 mg/day and vitamin D 800 IU/day
First Line
  • Bisphosphonates
    • Alendronate 10 mg PO daily or 70 mg PO weekly
    • Risedronate 5 mg PO daily, 35 mg PO weekly, 75 mg PO twice monthly, or 150 mg PO monthly
    • Ibandronate 150 mg PO once monthly or 3 mg IV every 3 months
    • Zoledronic acid 5 mg IV yearly
  • These drugs become incorporated into skeletal tissue, where they inhibit the resorption of bone by osteoclasts (3,4).
  • Alendronate, risedronate, and zoledronic acid reduce the incidence of vertebral and nonvertebral fractures while Ibandronate reduces vertebral fracture only.
  • The side effects are similar for all bisphosphonates and include gastrointestinal problems such as difficulty swallowing and inflammation of the esophagus and stomach.
  • Osteonecrosis of the jaw has been associated with bisphosphonates, particularly in patients with cancer who receive high doses (5).
  • There is a possible risk of midfemur fractures in patients receiving bisphosphonates for >5 years (6).
  • Avoid oral bisphosphonates in patients with
    • Delayed esophageal emptying
    • Inability to stand/sit upright for at least 30 to 60 minutes after taking the bisphosphonates
    • Hypocalcemia (correct prior to initiating therapy)
    • Severe renal impairment (creatine clearance [CrCI] ≤30 to 35 mL/min for alendronate, risedronate, and ibandronate and ≤35 mL/min for zoledronic acid)
Second Line
  • Raloxifene 60 mg PO daily
    • Selective estrogen receptor modulator with positive effects on BMD and vertebral fracture risk but no stimulatory action on breasts/uterus
    • Nonvertebral or hip fracture efficacy has not been demonstrated; increases risk of thromboembolism.
    • Additional side effects include menopausal symptoms (hot flashes and night sweats).
  • Teriparatide 20 mg SC daily
    • Recombinant formulation of PTH
    • Works anabolically to stimulate the growth of bone through osteoblastic activation
    • Studies have shown a reduction in the incidence of vertebral fractures by 65% and nonvertebral fractures by 53%.
    • No data exist on its safety and efficacy after >2 years of use (7).
  • Denosumab: 60 mg SQ every 6 months
    • Human monoclonal antibody receptor activator of nuclear factor kappa-B ligand (RANKL) receptor
    • Inhibits osteoclast formation
  • Estrogen 0.625 mg PO daily (with progesterone if patient has a uterus): effective in prevention and treatment of osteoporosis (34% reduction in hip and vertebral fractures after 5 years of use), but the risks (e.g., increased rates of myocardial infarction, stroke, breast cancer, pulmonary embolus, and deep vein thrombosis) must be weighed against the benefits
  • Strontium 2 g PO daily
    • Appears to inhibit bone resorption and increase bone formation
    • Available for use in Europe
  • Calcitonin
    • PTH antagonist that reduces osteoclastic activity, therefore decreasing bone turnover
    • FDA approved for treatment of osteoporosis in women who are at least 5 years postmenopausal when alternative treatments are not suitable.
    • Calcitonin reduces vertebral fracture occurence in those with prior vertebral.
    • Has been associated with an increased risk for malignancy
ISSUES FOR REFERRAL
Endocrinology for recurrent bone loss/fracture
ADDITIONAL THERAPIES
  • Weight-bearing exercise 30 minutes 3 times per week
  • Smoking cessation
  • Physical therapy to help with muscle strengthening
SURGERY/OTHER PROCEDURES
Options for patients with painful vertebral compression fractures failing medical treatment:
  • Vertebroplasty: Orthopedic cement is injected into the compressed vertebral body.
  • Kyphoplasty: A balloon is expanded within the compressed vertebral body to reconstruct volume of vertebrae. Cement is injected into the space.
COMPLEMENTARY & ALTERNATIVE MEDICINE
  • Isoflavones not better than placebo for fracture risk
  • Beneficial effect of Chinese herbal medicines in improving BMD is still uncertain.
INPATIENT CONSIDERATIONS
Admission Criteria/Initial Stabilization
Inpatient care for pain control of acute back pain secondary to new vertebral fractures and for acute treatment of femoral and pelvic fractures
Discharge Criteria
Rehabilitation, nursing home, or home care may be needed following hospitalization for fractures.
image ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
  • Weight-bearing exercises, such as walking, jogging, stair climbing, and tai chi, have been shown to decrease falls and fracture risk.
  • Yearly height measurement is essential to determination of osteoporosis treatment efficacy. Patients who lose >2 cm in height should have repeat vertebral imaging to determine if any new vertebral fractures have occurred (2).
  • While there is no consensus, most recommendations suggest BMD testing by DEXA scanning retesting 2 years after starting bisphosphonate therapy.
  • For many women, 3 to 5 years of treatment with a bisphosphonate is as good as 10 years of treatment.
  • A comprehensive risk assessment should be performed after 3 to 5 years of treatment. Those at high risk for vertebral fracture or with very low BMD may benefit by continuing treatment beyond 5 years.
  • Physicians prescribing bisphosphonates should advise patients of the small risk of osteonecrosis and encourage dental examinations (2).
DIET
  • Diet to maintain normal body weight
  • Calcium and vitamin D (see “General Prevention”)
PATIENT EDUCATION
National Osteoporosis Foundation: http://nof.org/
PROGNOSIS
  • With treatment, 80% of patients stabilize skeletal manifestations, increase bone mass and mobility, and have reduced pain.
  • 15% of vertebral and 20-40% of hip fractures may lead to chronic care and/or premature death.
REFERENCES
1. Christenson ES, Jiang X, Kagan R, et al. Osteoporosis management in post-menopausal women. Minerva Ginecol. 2012;64(3):181-194.
2. Cosman, F, de Beur SJ, LeBoff MS, et al. Clinician's guide to prevention and treatment of osteoporosis. Osteoporos Int. 2014;25(10):2359-2381.
3. Poole KE, Compston JE. Bisphosphonates in the treatment of osteoporosis. BMJ. 2012;344:e3211.
4. Heng C, Badner VM, Vakkas TG, et al. Bisphosphonate-related osteonecrosis of the jaw in patients with osteoporosis. Am Fam Physician. 2012;85(12):1134-1141.
5. McClung M, Harris ST, Miller PD, et al. Bisphosphonate therapy for osteoporosis: benefits, risk, and drug holiday. Am J Med. 2013;126(1):13-20.
6. Rao SS, Budhwar N, Ashfaque A. Osteoporosis in men. Am Fam Physician. 2010;82(5):503-508.
7. Gómez-de Diego R, Mang-de la Rosa M, Romero-Pérez MJ, et al. Indications and contraindications of dental implants in medically compromised patients: update. Med Oral Patol Oral Cir Bucal. 2014;19(5):e483-e489.
Codes
&NA;
ICD10
  • M81.0 Age-related osteoporosis w/o current pathological fracture
  • M80.00XA Age-rel osteopor w current path fracture, unsp site, init
  • M80.08XA Age-rel osteopor w current path fracture, vertebra(e), init
Clinical Pearls
&NA;
  • Screen all women ≥65 years of age with DEXA scans.
  • Premenopausal women with osteoporosis should be screened for secondary causes, such as malabsorption syndromes, hyperparathyroidism, hyperthyroidism, and medication sensitivity.
  • Evaluate and treat all patients presenting with fractures from minimal trauma.
  • Bisphosphonates are first line for treatment of osteoporosis in most patients.
  • If the patient is not responding to treatment, consider screening for a secondary, treatable cause of osteoporosis.