Musculoskeletal · PANCE / PANRE

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

WHO BMD classification by T-score and treatment thresholds.

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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