Osteoporosis¶
Chapter 423 | Part 12: Endocrinology
KEY CLINICAL POINTS¶
- Osteoporosis is defined by reduced bone strength and increased fracture risk, with WHO criteria using T-scores ≤ –2.5 for diagnosis.
- Postmenopausal women and elderly men are at highest risk, with 10.8 million in the US having osteoporosis and 40 million with osteopenia.
- Key risk factors include estrogen deficiency, vitamin D insufficiency, glucocorticoid use, and sedentary lifestyle.
- Bisphosphonates, denosumab, and teriparatide are first-line pharmacologic treatments for severe osteoporosis.
- FRAX tool assesses fracture risk combining BMD, age, and clinical risk factors for personalized treatment decisions.
1. DEFINITION & OVERVIEW¶
Osteoporosis is a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration, leading to increased fracture risk. WHO defines osteoporosis as a T-score ≤ –2.5 at lumbar spine, hip, or femoral neck. Osteopenia is T-score –1.0 to –2.5. Fragility fractures occur from minimal trauma and are central to diagnosis.
Table 423-1: Risk Factors for Osteoporosis Fracture¶
| NONMODIFIABLE | POTENTIALLY MODIFIABLE |
|---|---|
| Personal history of fracture as an adult | Current cigarette smoking |
| History of fracture in first-degree relative | Estrogen deficiency |
| Female gender | Early menopause (<45 years) or bilateral ovariectomy |
| Advanced age | Prolonged premenstrual amenorrhea (>1 year) |
| White race (>1 year) | Poor nutrition, especially low calcium and vitamin D intake |
| Dementia | Alcoholism |
| Impaired eyesight despite adequate correction | Recurrent falls |
| Inadequate physical activity | Poor health/frailty |
1.1 Diagnostic Criteria¶
WHO criteria: T-score ≤ –2.5 (osteoporosis) or –1.0 to –2.5 (osteopenia). FRAX tool integrates BMD with clinical risk factors for fracture probability.
1.2 Bone Microarchitecture¶
Loss of trabecular bone and cortical thinning disrupts bone strength. DXA measures BMD, but advanced tools like HR-pQCT assess microarchitecture.
2. EPIDEMIOLOGY¶
10.8 million adults in the US have osteoporosis (BMD T-score <–2.5). 40 million have osteopenia (T-score –1.0 to –2.5). 2 million fractures annually, costing $19 billion. Hip fractures: 300,000/year, 14% lifetime risk for women, 5% for men. Mortality: 20–25% within 1 year post-fracture.
Table 423-2: Diseases Associated with Generalized Osteoporosis¶
| Category | Examples |
|---|---|
| Hypogonadal states | Turner’s syndrome, Klinefelter’s syndrome, hypogonadism |
| Endocrine disorders | Cushing’s syndrome, hyperparathyroidism, diabetes mellitus |
| Nutritional disorders | Malnutrition, celiac disease, parenteral nutrition |
| Chronic diseases | Rheumatoid arthritis, Crohn’s disease, chronic obstructive pulmonary disease |
| Genetic disorders | Osteogenesis imperfecta, Marfan’s syndrome, hemochromatosis |
| Other | Hematologic malignancies, chronic kidney disease, immobilization |
2.1 Age and Sex¶
Most fractures occur in postmenopausal women (50% of osteoporotic fractures) and elderly men. Women have higher fracture risk due to lower peak bone mass and rapid postmenopausal bone loss.
2.2 Ethnicity¶
White race is a risk factor, but African Americans have lower osteoporosis risk due to better calcium homeostasis.
3. ETIOLOGY & PATHOPHYSIOLOGY¶
Bone remodeling imbalance (resorption > formation) due to hormonal, genetic, and environmental factors. Key mechanisms: estrogen deficiency, vitamin D insufficiency, glucocorticoid use, and reduced physical activity.
Table 423-3: Drugs Associated with Generalized Osteoporosis¶
| Drug Class | Examples |
|---|---|
| Glucocorticoids | Prednisone, dexamethasone |
| Anticonvulsants | Phenytoin, carbamazepine |
| Aromatase inhibitors | Anastrozole, letrozole |
| Selective serotonin reuptake inhibitors | Sertraline, paroxetine |
| Thiazolidinediones | Rosiglitazone, pioglitazone |
| Androgen deprivation therapy | LHRH agonists, testosterone suppression |
3.1 Bone Remodeling¶
RANKL/RANK/OPG pathway regulates osteoclast activity. Estrogen deficiency increases RANKL and decreases osteoprotegerin, enhancing bone resorption.
3.2 Vitamin D Role¶
Vitamin D deficiency causes secondary hyperparathyroidism, increasing bone resorption. Supplementation (1000–1200 mg/day) is recommended for adults.
4. CLINICAL FEATURES¶
Silent disease until fracture occurs. Common fractures: vertebral (70% asymptomatic), hip, wrist, and Colles’ fractures. Symptoms: height loss, kyphosis, back pain, and increased fall risk.
4.1 Fracture Patterns¶
Vertebral fractures: height loss, kyphosis. Hip fractures: groin pain, inability to bear weight. Wrist fractures: pain, swelling, deformity.
4.2 Complications¶
Increased mortality (20–25% within 1 year), long-term disability, and increased risk of subsequent fractures.
5. DIFFERENTIAL DIAGNOSIS¶
Secondary causes include hypogonadism, hyperparathyroidism, malabsorption, and malignancy. Distinguish from osteomalacia and Paget’s disease.
5.1 Secondary Causes¶
Hypogonadism, malabsorption syndromes, chronic kidney disease, and glucocorticoid use.
5.2 Imaging Findings¶
Vertebral fractures on X-ray, decreased trabecular bone on DXA, and cortical thinning on HR-pQCT.
6. INVESTIGATIONS & DIAGNOSIS¶
DXA for BMD (T-score <–2.5 = osteoporosis). FRAX tool estimates 10-year fracture risk. Biochemical markers (CTX, P1NP) assess bone turnover.
Table 423-4: Indications for Bone Mineral Density Testing¶
| Indication |
|---|
| Women ‡65 and men ‡70 regardless of risk factors |
| Postmenopausal women with clinical risk factors |
| Adults with fractures ‡50 years old |
| Patients with conditions (e.g., rheumatoid arthritis) or medications (e.g., glucocorticoids >5 mg prednisone) |
6.1 Diagnostic Tests¶
DXA (lumbar spine, hip), FRAX algorithm, and biochemical markers (serum calcium, PTH, 25(OH)D).
6.2 Bone Density Testing¶
Indicated for postmenopausal women ≥ 65, men ≥ 70, or those with fractures ≥ 50 years old. T-score <–1.5 in spine/hip requires vertebral imaging.
7. MANAGEMENT & TREATMENT¶
Pharmacologic: bisphosphonates, denosumab, teriparatide. Non-pharmacologic: calcium/vitamin D, exercise, fall prevention. Treatment thresholds: 20% 10-year fracture risk or 3% hip fracture risk.
Table 423-5: Indications for Vertebral Testing¶
| Indication |
|---|
| All women ‡70 and men ‡80 with T-score <1.0 at spine/hip/femoral neck |
| Women 65–69 and men 70–79 with T-score <1.5 at spine/hip/femoral neck |
| Postmenopausal women/men ‡50 with specific risk factors (e.g., fragility fracture, height loss ‡1.5 in.) |
7.1 Pharmacologic Therapies¶
Bisphosphonates (alendronate, risedronate), denosumab (RANKL inhibitor), teriparatide (PTH analog), and romosozumab (sclerostin inhibitor).
7.2 Non-Pharmacologic¶
Calcium (1000–1200 mg/day), vitamin D (600–800 IU/day), weight-bearing exercise, and fall prevention strategies.
8. PROGNOSIS & COMPLICATIONS¶
High fracture risk persists with aging. Complications include mortality, disability, and increased risk of subsequent fractures. Atypical femoral fractures and MRONJ are rare but serious side effects of bisphosphonates.
8.1 Fracture Risk¶
50% of fractures occur in osteopenia (T-score –1.0 to –2.5). 10-year fracture risk >20% or >3% for hip requires treatment.
8.2 Adverse Effects¶
Atypical femoral fractures (stress fractures), MRONJ (jaw necrosis), and hypocalcemia with bisphosphonates.
9. SPECIAL CONSIDERATIONS¶
Pregnancy: calcium/vitamin D supplementation. Pediatrics: growth-related bone mass. Elderly: fall prevention. Special populations: glucocorticoid users, cancer patients, and those with chronic diseases.
9.1 Pregnancy¶
Calcium (1300 mg/day) and vitamin D (600 IU/day) recommended. Avoid bisphosphonates.
9.2 Elderly¶
Fall prevention, vitamin D supplementation, and regular BMD monitoring.
10. KEY POINTS & CLINICAL PEARLS¶
- Osteoporosis is a major public health issue with 10.8 million cases in the US. 2. FRAX tool integrates BMD and clinical risk factors for fracture prediction. 3. Bisphosphonates are first-line for most patients, while teriparatide/romosozumab are for severe cases. 4. Calcium (1000–1200 mg/day) and vitamin D (600–800 IU/day) are essential for bone health. 5. Fall prevention and exercise are critical non-pharmacologic interventions.