Osteoporosis
Skeletal disorder of reduced bone strength and increased fracture risk; managed with bone-protective lifestyle and antiresorptive or anabolic therapy.
Also known as: osteoporosis, low bone density, fragility fracture
Overview
Skeletal disorder characterized by compromised bone strength predisposing to fracture. Defined operationally by bone mineral density T-score ≤ -2.5 at the femoral neck, total hip, or lumbar spine, OR by the occurrence of a fragility fracture (low-energy fracture from a fall from standing height or less). T-score between -1.0 and -2.5 is osteopenia (low bone mass).
Epidemiology
Affects ~10 million US adults; estimated 50% of women and 20% of men over 50 will have an osteoporotic fracture in their lifetime. Hip fractures carry ~20-30% 1-year mortality.
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Risk factors
- Non-modifiable: age >65, female sex, postmenopausal status, white or Asian ancestry, family history of hip fracture, low body weight, prior fragility fracture
- Modifiable: tobacco use, excessive alcohol (>3 drinks/day), low calcium and vitamin D intake, sedentary lifestyle
- Medications: chronic glucocorticoids (≥5 mg prednisone for ≥3 months), aromatase inhibitors, androgen deprivation, PPIs, SSRIs, anticonvulsants, heparin, thiazolidinediones
- Endocrine: hyperthyroidism, hyperparathyroidism, hypogonadism, Cushing syndrome, type 1 diabetes
- GI: celiac disease, IBD, bariatric surgery, malabsorption
- Other: rheumatoid arthritis, chronic kidney/liver disease, multiple myeloma, anorexia nervosa, hypercalciuria
Pathophysiology
Bone is in continuous turnover via osteoclast-mediated resorption and osteoblast-mediated formation. After peak bone mass (~age 30), resorption progressively exceeds formation. Estrogen withdrawal at menopause sharply increases osteoclast activity. Secondary causes (glucocorticoids, hyperparathyroidism) act through additional mechanisms — direct osteoblast suppression, increased RANKL signaling, and accelerated remodeling. The result is reduced trabecular connectivity and cortical thinning.
Clinical presentation
Symptoms
- Asymptomatic until fracture occurs
- Vertebral compression fracture: sudden back pain after minor strain, often spontaneous; can be silent
- Loss of height >1.5 inches (4 cm) and progressive thoracic kyphosis
- Hip, distal radius (Colles), pelvis, or proximal humerus fracture from low-energy fall
Signs / physical exam
- Thoracic kyphosis ('dowager hump')
- Loss of height
- Rib-pelvis distance <2 finger-breadths
- Tenderness to percussion over a fractured vertebra
Differential diagnosis
- Osteomalacia — Defective mineralization from vitamin D deficiency or hypophosphatemia; bone pain, proximal weakness; low Ca, low phos, elevated alk phos, low 25-OH vitamin D
- Multiple myeloma — Bone pain, anemia, hypercalcemia, renal dysfunction; lytic lesions; SPEP/UPEP, free light chains
- Metastatic bone disease — Known cancer or unexplained focal pain; lytic or blastic lesions; isolated fracture out of proportion
- Hyperparathyroidism — Hypercalcemia, elevated PTH, subperiosteal resorption on imaging
- Paget disease — Elevated alk phos with normal Ca/phos; bony enlargement and deformity; characteristic mosaic pattern on biopsy
- Osteogenesis imperfecta — Childhood-onset fractures, blue sclerae, hearing loss, family history
Diagnostic workup
Labs
- CBC, BMP, Ca, phos, Mg, 25-OH vitamin D, alkaline phosphatase
- TSH, intact PTH
- 24-hour urine calcium and creatinine (rule out hypercalciuria, malabsorption)
- Testosterone in men
- Celiac serologies if anemia or low BMI
- SPEP/UPEP/free light chains if anemia, renal dysfunction, or atypical fracture pattern
- Bone turnover markers (CTX, P1NP) — useful for monitoring response, not for diagnosis
Imaging
- Central DXA at lumbar spine and total hip (femoral neck) — diagnostic test
- Vertebral fracture assessment (VFA) or lateral spine radiograph to detect silent vertebral fractures
- FRAX calculator for 10-year fracture risk estimation
Diagnostic algorithm
| T-score Category | Definition | Action |
|---|---|---|
| Normal | ≥ -1.0 | Lifestyle counseling; rescreen per guideline |
| Osteopenia (low bone mass) | -1.0 to -2.5 | Use FRAX; treat if FRAX ≥3% hip / ≥20% major OP fx |
| Osteoporosis | ≤ -2.5 | Pharmacologic therapy + Ca / vit D / exercise |
| Severe (established) osteoporosis | ≤ -2.5 + fragility fracture | Same as above; consider anabolic agent if very high risk |
Complications
- Hip, vertebral, distal radius, and other fragility fractures
- Chronic pain, kyphosis, loss of height, reduced pulmonary function
- Functional decline, dependency, increased mortality (especially after hip fracture)
- Atypical femoral fracture (rare; long-term bisphosphonate or denosumab use)
- Osteonecrosis of the jaw (rare; especially with dental procedures during high-dose IV bisphosphonate or denosumab)
PANCE pearls
- Treat the patient, not just the T-score: a history of fragility fracture is sufficient to diagnose and treat osteoporosis regardless of DXA.
- Denosumab requires uninterrupted dosing — discontinuation without a bisphosphonate bridge causes rapid bone loss and multiple vertebral fractures.
- FRAX score guides treatment thresholds in patients with osteopenia.
- Anabolic therapy first in very high-risk patients yields greater BMD gains than antiresorptive-first; always follow with antiresorptive.
- Always evaluate for and treat secondary causes — about 30% of women and 50% of men with osteoporosis have a contributing secondary cause.
References
- USPSTF 2018 — USPSTF Recommendation Statement: Osteoporosis to Prevent Fractures (JAMA 2018)
- NOF/BHOF 2022 — Clinician's Guide to Prevention and Treatment of Osteoporosis (Bone Health & Osteoporosis Foundation, 2022)
- Endocrine Society 2019/2020 — Pharmacological Management of Osteoporosis in Postmenopausal Women: Endocrine Society Clinical Practice Guideline (Eastell et al., J Clin Endocrinol Metab 2019; 2020 update)
- ACR 2017 — ACR Guideline for Prevention and Treatment of Glucocorticoid-Induced Osteoporosis (Buckley et al., Arthritis Rheumatol 2017)
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