Risks Related to Osteoporosis
Osteoporosis significantly increases fracture risk, with postmenopausal women facing a 50% lifetime probability of sustaining an osteoporosis-related fracture, and hip fractures carry substantial mortality—over one-third of men die within 1 year of hip fracture. 1
Major Fracture-Related Risks
Mortality and Morbidity
- Hip fractures are associated with the highest mortality risk, with more than one-third of men dying within 1 year following hip fracture 1
- Vertebral fractures occur in 25% of postmenopausal women who sustain any osteoporotic fracture 1
- Hip fractures occur in 15% of women with osteoporotic fractures and are associated with chronic pain, disability, loss of independence, and decreased quality of life 1
- From age 50 to 90, hip fracture risk increases 50-fold and vertebral fracture risk increases 15- to 30-fold in white women 1
Fracture Probability by Population
- Approximately 40% of 50-year-old women will sustain one or more osteoporosis-related fractures (spine, hip, or wrist) during their remaining lifetime 1
- One in three postmenopausal women and one in five older men experience osteoporotic fractures in their lifetime 2
- By 2012, approximately 12 million Americans older than 50 years were expected to have osteoporosis 1
Clinical Risk Factors That Amplify Fracture Risk
Non-Modifiable Risk Factors
- Increasing age is the strongest determinant of fracture risk, even stronger than bone mineral density alone 1
- Female sex and postmenopausal status 1
- White ethnicity (higher risk than Black persons) 1
- History of parental hip fracture 1
- Previous clinical or morphometric vertebral fracture 1
- Previous fragility fracture (fracture from minimal trauma) 1
Modifiable Risk Factors
- Low body weight (<70 kg) is the single best predictor of low bone mineral density 1
- Current smoking 1
- Alcohol intake of 3 or more drinks daily 1
- Vitamin D deficiency 1
- Low calcium intake 1
- Physical inactivity and immobilization 1
- Hyperkyphosis 1
- History of falls 1
Medical Conditions Increasing Risk
- Rheumatoid arthritis 1
- Hypogonadism or premature ovarian failure 1
- Inflammatory bowel disease 2
- Chronic liver and kidney disease 2
Medication-Related Risks
- Long-term glucocorticoid use (≥5 mg prednisone daily for ≥3 months) is the most commonly implicated medication 1
- Anticoagulants 1
- Anticonvulsants 1
- Aromatase inhibitors 1
- Cancer chemotherapeutic drugs 1
- Gonadotropin-releasing hormone agonists 1
Cancer Treatment-Specific Risks
Hormone Deprivation Therapy
- Androgen deprivation therapy for prostate cancer increases bone loss and fracture risk 3
- Aromatase inhibitor therapy for breast cancer increases bone loss and fracture risk 3
- Women with breast cancer have vertebral fracture risk 4.7 times higher with localized disease and 22.7 times higher with soft tissue metastasis compared to women without cancer 4
Chemotherapy-Induced Effects
- Chemotherapy-induced menopause accelerates bone loss 1
- Glucocorticoids used as premedications or antiemetics in cancer treatment contribute to bone loss 1
Racial and Ethnic Disparities in Fracture Risk
- Asian, Black, and Hispanic populations have lower fracture incidence compared to White populations, despite sometimes having lower bone mineral density 1
- Asian women have lower BMD than White women but paradoxically lower fracture risk 1
- These differences are likely due to social, environmental factors, and differences in clinical risks beyond BMD alone 1
Limitations of Bone Mineral Density as Risk Predictor
- Low BMD measured by DXA identifies less than half of people who will sustain an osteoporotic fracture 1
- Advancing age increases fracture rates even at the same BMD level due to declining bone quality and increased fall risk 1
- Fracture risk increases two to threefold for each standard deviation decrease in BMD 1
Management Implications to Reduce Risk
Screening Recommendations
- All women aged 65 years and older should be screened routinely 1
- Women aged 60-64 years with risk factors (particularly low body weight <70 kg, no current estrogen use) should be screened 1
- Postmenopausal women younger than 65 years with one or more risk factors should undergo risk assessment using clinical tools like FRAX 1
Pharmacologic Risk Reduction
- For women with known osteoporosis, alendronate, risedronate, zoledronic acid, or denosumab reduce hip and vertebral fracture risk 1
- Bisphosphonates reduce vertebral fractures by 52 per 1000 person-years and hip fractures by 6 per 1000 person-years 2
- Denosumab reduces incidence of vertebral, nonvertebral, and hip fractures in postmenopausal women 3
- For very high-risk individuals (recent vertebral fractures, hip fracture with T-score ≤-2.5), anabolic medications (teriparatide, abaloparatide, romosozumab) should be considered first, followed by antiresorptive agents 2
Non-Pharmacologic Risk Reduction
- Adequate calcium intake (1000-1200 mg daily) and vitamin D (600-800 IU daily) 2
- Weight-bearing and muscle resistance exercises (squats, push-ups) 2
- Balance exercises (heel raises, standing on one foot) 2
- Smoking cessation 5
- Moderation of alcohol intake 5
Common Pitfalls in Risk Assessment
- Do not rely solely on BMD T-scores—advancing age and clinical risk factors are equally or more important predictors 1
- Osteoporosis remains completely asymptomatic until fracture occurs, requiring proactive screening rather than waiting for symptoms 6
- Patients with advanced chronic kidney disease (eGFR <30 mL/min/1.73 m²) are at greater risk of severe hypocalcemia with denosumab treatment and require specialized management 3
- Drug holidays after 5 years of alendronate or 3 years of zoledronic acid may be considered for lower-risk patients, as benefits are retained after discontinuation 7