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Endocrinology›Condition·Updated Jun 28, 2026·v1

Osteoporosis

Osteoporosis is a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration, leading to increased fracture risk. Diagnosis is based on DXA T-score ≤ -2.5 or a fragility fracture. Management includes calcium/vitamin D supplementation, weight-bearing exercise, fall prevention, and pharmacotherapy with antiresorptive agents (bisphosphonates, denosumab) or anabolic agents (teriparatide, romosozumab) for high-risk patients. Early treatment reduces fracture risk by up to 70%.

High Evidence95 references·11,188 words·45 min read·v1
osteoporosisbone mineral densityfracture preventionbisphosphonatesdenosumabteriparatideromosozumabFRAXDXApostmenopausal osteoporosisglucocorticoid-induced osteoporosisfragility fracture

Quick Reference

RxDrug of choiceAlendronate 70 mg orally once weekly (first-line antiresorptive) or zoledronic acid 5 mg IV yearly for patients who cannot tolerate oral therapy.
AltAlternativesDenosumab 60 mg SC every 6 months; teriparatide 20 mcg SC daily (anabolic, 24-month limit); romosozumab 210 mg SC monthly (dual-action, 12-month limit); raloxifene 60 mg daily (SERM, for postmenopausal women only).
⊘AvoidBisphosphonates in eGFR <35 mL/min; romosozumab within 1 year of MI or stroke; teriparatide/abaloparatide in Paget disease, prior skeletal radiation, or open epiphyses; raloxifene in patients with history of VTE.
DxTest of choiceDual-energy X-ray absorptiometry (DXA) of lumbar spine and hip; T-score ≤ -2.5 is diagnostic.
ScKey scoreFRAX (Fracture Risk Assessment Tool), 10-year probability of major osteoporotic fracture and hip fracture.
→When to referFragility fracture at any site; very high fracture risk (T-score ≤ -3.0, recent fracture, multiple fractures); suspected secondary cause; failure of first-line therapy; consideration of anabolic agents.
Osteoporosis is a silent disease until fracture occurs; diagnose with DXA T-score ≤ -2.5 or fragility fracture; treat with bisphosphonates or denosumab as first-line, and consider anabolics for very high-risk patients; always ensure calcium/vitamin D, exercise, and fall prevention.
Osteoporosis is a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration, leading to increased fracture risk. It affects an estimated 200 million women worldwide and causes over 8.9 million fractures annually. The diagnosis is established by a T-score ≤ -2.5 on dual-energy X-ray absorptiometry (DXA) or by the presence of a fragility fracture. Management includes non-pharmacologic measures (calcium, vitamin D, exercise, fall prevention) and pharmacotherapy with antiresorptive agents (bisphosphonates, denosumab) or anabolic agents (teriparatide, romosozumab) for high-risk patients. Early identification and treatment reduce fracture risk by up to 70%.

Overview and Recommendations

Background

  • •Osteoporosis is a systemic skeletal disease defined by low bone mass and microarchitectural deterioration of bone tissue, leading to enhanced bone fragility and a consequent increase in fracture risk. It is the most common metabolic bone disease worldwide, affecting an estimated 200 million women and causing over 8.9 million fractures annually, one fracture every 3 seconds.
  • •Postmenopausal osteoporosis (Type I) occurs in women within 15-20 years of due to estrogen-deficiency-driven accelerated bone loss, preferentially affecting trabecular bone (vertebrae, distal forearm). Senile osteoporosis (Type II) affects both sexes after age 70-75 due to age-related decline in bone formation, decreased calcium absorption, and , involving both cortical and trabecular bone.
  • •Secondary osteoporosis results from an identifiable cause such as glucocorticoid therapy (≥5 mg/day equivalent for ≥3 months), aromatase inhibitors, hypogonadism, hyperthyroidism, hyperparathyroidism, malabsorption (celiac disease, inflammatory bowel disease), chronic kidney disease, or immobilization. Up to 30% of men and 50% of premenopausal women with osteoporosis have an underlying secondary cause.
  • •The WHO operational definition uses bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA): T-score ≤ -2.5 defines osteoporosis; T-score between -1.0 and -2.5 defines osteopenia (low bone mass). The -2.5 threshold identifies approximately 30% of postmenopausal women at the hip, correlating with lifetime fracture risk. A clinical diagnosis can also be made in the presence of a fragility fracture regardless of T-score.
  • •Following a , mortality is 20-24% in the first year, and many survivors lose independent mobility. A prior fragility fracture is the single strongest predictor of a subsequent fracture, doubling the risk independent of BMD. The disease is underdiagnosed, especially in men and special populations such as adults with cerebral palsy.

Evaluation

  • •Suspect osteoporosis in any patient aged ≥50 with a low-trauma (fragility) fracture, one resulting from a fall from standing height or less, or from routine activities such as bending or coughing. Classic fracture sites are the hip (proximal femur), vertebral body (spine), and distal forearm (wrist); also consider fractures of the humerus, pelvis, ribs, and tibia as osteoporotic.
  • •Ask about prior fragility fractures, parental history of hip fracture, current smoking, alcohol intake (≥3 units/day), glucocorticoid use (≥5 mg prednisolone daily for ≥3 months), and secondary causes such as rheumatoid arthritis, type 1 diabetes, hyperthyroidism, hypogonadism, chronic liver disease, and malabsorption. In women, document menopausal status and age at menopause.
  • •Examine for height loss (measure against prior records), kyphosis (dowager's hump), rib-to-pelvis distance ≤2 fingerbreadths on lateral inspection, and signs of vertebral compression (acute back pain with band-like radiation, worsened by weight-bearing, relieved by lying flat). Two-thirds of vertebral fractures are clinically silent.
  • •Order central dual-energy X-ray absorptiometry (DXA) of the lumbar spine and hip as the gold-standard diagnostic test. The femoral neck and total hip are standard sites for diagnosis and monitoring; the forearm (33% radius) is used when spine or hip cannot be measured or in hyperparathyroidism. Peripheral DXA or quantitative ultrasound (QUS) of the heel can be used for initial risk stratification but are not diagnostic.
  • •Diagnostic criteria: T-score ≤ -2.5 at the lumbar spine, total hip, or femoral neck defines osteoporosis. A T-score between -1.0 and -2.5 indicates osteopenia. In patients with a fragility fracture and T-score > -2.5, a clinical diagnosis of osteoporosis can still be made based on fracture history.
  • •Calculate the 10-year fracture probability using the FRAX tool (Fracture Risk Assessment Tool) in patients with osteopenia or those aged 40-90 with risk factors. FRAX integrates 12 clinical risk factors with or without femoral neck BMD. Most guidelines recommend pharmacotherapy when the 10-year major osteoporotic fracture probability exceeds 20% or the hip fracture probability exceeds 3%.
  • •Also consider alternative imaging: quantitative computed tomography (QCT) for volumetric BMD, high-resolution peripheral QCT (HR-pQCT) for microarchitecture assessment, and artificial intelligence (AI) algorithms that derive BMD from routine radiographs (opportunistic screening). These are not first-line but useful when DXA is unavailable.
  • •Evaluate for secondary causes in all patients with osteoporosis, especially if BMD is unexpectedly low or declines rapidly. Initial laboratory evaluation includes serum calcium, phosphate, alkaline phosphatase, creatinine, 25-hydroxyvitamin D, intact PTH, thyroid-stimulating hormone (TSH), testosterone (in men), 24-hour urinary calcium, celiac serology, and serum protein electrophoresis (if vertebral fractures or anemia suggest ).
  • •In patients with suspected primary hyperparathyroidism, include forearm DXA because up to 20% have osteoporosis isolated to the distal radius. Forearm DXA is also recommended in hyperparathyroidism to detect cortical bone loss.
  • •Assess fall risk as part of the evaluation: ask about falls in the past year, review medications that increase fall risk (sedatives, antihypertensives, anticholinergics), and perform a simple balance test (e.g., timed up-and-go). Multifactorial fall prevention programs reduce fall rates by 25-30%.

Management

  • •Ensure adequate calcium and vitamin D intake: total daily calcium (diet plus supplement) 1000-1200 mg; vitamin D 800-1000 IU/day for adults aged ≥50. Supplement only in patients with low dietary intake; exceeding 1200 mg/day calcium provides no additional benefit and may increase risk of nephrolithiasis and cardiovascular events.
  • •Prescribe weight-bearing aerobic exercise (30-45 minutes, 4-5 days/week) and resistance training (2-3 days/week) to improve BMD, muscle strength, and balance. Walking ≥30 min/day is associated with a 20% lower hazard of incident osteoporosis. Balance training (tai chi, yoga) reduces fall risk.
  • •Implement multifactorial fall prevention: medication review (deprescribe sedatives, antihypertensives), home safety assessment (remove loose rugs, improve lighting, install grab bars), vision correction, and appropriate footwear.
  • •Initiate pharmacotherapy in patients with T-score ≤ -2.5, or prior hip or vertebral fracture, or T-score between -1.0 and -2.5 with FRAX 10-year major fracture risk ≥20% or hip fracture risk ≥3%. First-line antiresorptive therapy: alendronate 70 mg orally once weekly, risedronate 35 mg orally once weekly (or 150 mg monthly), or zoledronic acid 5 mg intravenously once yearly.
  • •Alternative antiresorptive: denosumab 60 mg subcutaneously every 6 months. Denosumab is preferred in patients with renal impairment (eGFR <35 mL/min) where bisphosphonates are contraindicated. Monitor serum calcium before each dose; correct hypocalcemia and ensure adequate vitamin D. Do not stop denosumab without transitioning to a bisphosphonate to prevent rebound vertebral fractures.
  • •For patients at very high fracture risk (T-score ≤ -3.0, recent fragility fracture, multiple fractures, or FRAX major fracture probability >20%), consider first-line anabolic or dual-action therapy: teriparatide 20 mcg subcutaneously daily (lifetime limit 24 months), abaloparatide 80 mcg subcutaneously daily (24-month limit), or romosozumab 210 mg subcutaneously monthly (12-month limit).
  • •Romosozumab is contraindicated in patients with a history of myocardial infarction or stroke within the preceding year due to increased risk of major adverse cardiovascular events (MACE). Teriparatide and abaloparatide are contraindicated in Paget disease, prior radiation to the skeleton, or open epiphyses due to osteosarcoma risk.
  • •After completing an anabolic or dual-action course (12-24 months), transition immediately to a potent antiresorptive (denosumab or zoledronic acid) to preserve gained bone. The optimal transition window is within one month of the last dose.
  • •Monitor BMD by DXA every 1-2 years after initiating therapy until stable, then every 2 years. Use bone turnover markers (P1NP for formation, CTX-1 for resorption) at 3-6 months to confirm adherence and response: a decrease in CTX-1 ≥30% (antiresorptive) or increase in P1NP ≥30% (anabolic) correlates with subsequent BMD improvement.
  • •For bisphosphonates, reassess fracture risk after 3-5 years. In low-risk patients (T-score > -2.5, no fractures), consider a drug holiday of 2-3 years. High-risk patients may continue for up to 10 years. During a drug holiday, monitor BMD every 2 years; resume therapy if BMD drops by more than the least significant change or if a fragility fracture occurs.
  • •Denosumab should not be interrupted without bridging to an antiresorptive. If therapy is stopped, initiate a bisphosphonate at the time of the next missed dose to prevent rebound vertebral fractures.
  • •Avoid non-dihydropyridine calcium channel blockers (diltiazem, verapamil) in patients with heart failure, but this is not specific to osteoporosis. In osteoporosis, avoid combining PTH analogs with romosozumab (no trial support, theoretical additive risk). Avoid exceeding the 24-month lifetime limit for PTH analogs.
  • •Refer to an endocrinologist or rheumatologist for patients with unexplained osteoporosis (especially men, premenopausal women, or those with multiple fractures despite therapy), suspected secondary causes requiring further workup, or when considering anabolic therapy. Refer to a fracture liaison service if available for coordinated post-fracture care.
  • •Discharge criteria for hospitalized patients with fragility fracture: ensure initiation of bone-protective therapy (if indicated), calcium/vitamin D supplementation, fall prevention education, and follow-up with primary care or specialist within 4-6 weeks for DXA and treatment plan.

Board Review — High Yield

  • •Fragility fracture, A fracture from a fall from standing height or less; the strongest predictor of future fracture, doubling risk independent of BMD.
  • •T-score ≤ -2.5, WHO diagnostic threshold for osteoporosis; identifies ~30% of postmenopausal women at the hip.
  • •FRAX, 10-year fracture probability tool integrating 12 clinical risk factors ± femoral neck BMD; treatment threshold typically ≥20% major fracture or ≥3% hip fracture.
  • •Bisphosphonates, First-line antiresorptive; alendronate 70 mg weekly, risedronate 35 mg weekly, zoledronic acid 5 mg yearly; drug holiday after 3-5 years in low-risk patients.
  • •Denosumab, RANKL inhibitor 60 mg SC every 6 months; superior BMD gains but requires uninterrupted therapy; rebound fractures if stopped without bridging to bisphosphonate.
  • •Anabolic agents, Teriparatide (PTH analog) 20 mcg SC daily, abaloparatide 80 mcg SC daily, romosozumab (sclerostin inhibitor) 210 mg SC monthly; reserved for very high fracture risk; lifetime limit 24 months for PTH analogs, 12 months for romosozumab.
  • •Romosozumab contraindication, History of MI or stroke within 1 year due to MACE risk (FDA black-box warning).
  • •Secondary osteoporosis, Up to 30% of men and 50% of premenopausal women have an identifiable cause; common causes: glucocorticoids, aromatase inhibitors, hypogonadism, hyperparathyroidism, malabsorption.
  • •Calcium and vitamin D, Total calcium intake 1000-1200 mg/day; vitamin D 800-1000 IU/day; supplementation only beneficial in those with low dietary intake or deficiency.
  • •Fall prevention, Multifactorial programs reduce falls by 25-30%; include medication review, home safety, vision correction, balance training.

Deep Dive — Evidence Details

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