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E42 Endocrinology
Metabolic Bone Disease
Toronto Notes 2019
Aledronate (10 mg/d)
1° Prevention – Vertebral (Gold) 1° Prevention – Hip
1° Prevention – Wrist
2° Prevention – Vertebral (Gold) 2° Prevention – Hip (Gold)
2° Prevention – Wrist (Gold)
Etidronate (400 mg/d)
1° Prevention – Vertebral
1° Prevention – Hip
1° Prevention – Wrist
2° Prevention – Vertebral (Silver) 2° Prevention – Hip
2° Prevention – Wrist
Risedronate (5 mg/d)
1° Prevention – Vertebral
1° Prevention – Hip
1° Prevention – Wrist
2° Prevention – Vertebral (Gold) 2° Prevention – Hip (Silver)
2° Prevention – Wrist
45% RRR, 2% ARR Not significant Not significant 45% RRR, 6% ARR 53% RRR, 1% ARR 50% RRR, 2% ARR
Not significant Not significant Not significant 47% RRR, 5% ARR No benefit
No benefit
Not significant Not significant Not significant 39% RRR, 5% ARR 26% RRR, 1% ARR Not significant
Table 32. Indications for BMD Testing
Older Adults (age ≥50 yr)
All women and men age ≥65 yr
Menopausal women, and men aged 50-64 yr with clinical risk factors for fracture:
Fragility fracture after age 40
Prolonged glucocorticoid use
Other high-risk medication use (aromatase inhibitors, androgen deprivation therapy) Parental hip fracture
Vertebral fracture or osteopenia identified on x-ray
Current smoking
High alcohol intake
Low body weight (<60 kg) or major weight loss (>10% of weight at age 25 yr) Rheumatoid arthritis
Other disorders strongly associated with osteoporosis: primary hyperparathyroidism, Type 1 DM, osteogenesis imperfecta, uncontrolled hyperthyroidism, hypogonadism or premature menopause (<45 yr), Cushing’s disease, chronic malnutrition or malabsorption, chronic liver disease, COPD, and chronic inflammatory conditions (e.g. inflammatory bowel disease)
Table 33. Osteoporisis Risk Stratification
Younger Adults (age <50 yr)
Fragility fracture
Prolonged use of glucocorticoids
Use of other high-risk medications (aromatase inhibitors, androgen deprivation therapy, anticonvulsants) Hypogonadism or premature menopause Malabsorption syndrome
Primary hyperparathyroidism
Other disorders strongly associated with rapid bone loss and/or fracture
Factors Necessary for Mineralization
• Quantitatively and qualitatively normal osteoid formation
• Normal concentration of calcium and phosphate in ECF
• Adequate bioactivity of ALP
• Normal pH at site of calcification
• Absence of inhibitors of calcification
High Risk
10 yr fracture risk >20%; OR
Prior fragility fracture of hip or spine; OR More than one fragility fracture
Treatment of Osteoporosis
Low Risk
10 yr fracture risk <10%
Medium Risk
10 yr fracture risk 10-20%
Unlikely to benefit from pharmacotherapy; encourage lifestyle changes Reassess risk in 5 yr
Discuss patient preference for management and consider additional risk factors Factors that warrant consideration for pharmacological therapy:
Additional vertebral fracture(s) identified on vertebral fracture assessment (VFA) or lateral spine x-ray
Previous wrist fracture in individuals ≥65 or with T-score ≤–2.5
Lumbar spine T-score much lower than femoral neck T-score
Rapid bone loss
Men receiving androgen-deprivation therapy for prostate cancer
Women receiving aromatase-inhibitor therapy for breast cancer
Long-term or repeated systemic glucocorticoid use (oral or parenteral) that does not meet the conventional criteria for recent prolonged systemic glucocorticoid use Recurrent falls (defined as falling 2 or more times in the past 12 mo)
Other disorders strongly associated with osteoporosis
Repeat BMD and reassess risk every 1-3 yr initially Start pharmacotherapy
Table 34. Treatment of Osteoporosis in Women and Men
Treatment for Both Men and Women
Lifestyle
Drug Therapy
Bisphosphonate: inhibitors of osteoclast binding
RANKL Inhibitors
Parathyroid Hormone (teriparatide)
Diet: Elemental calcium 1000-1200 mg/d; Vit D 1000 IU/d
Exercise: 3x30 min weight-bearing exercises, balance exercise, and aerobic exercise/wk Cessation of smoking, reduce caffeine intake
Stop/avoid osteoporosis-inducing medications
1st line in prevention of hip, nonvertebral, and vertebral # (Grade A): alendronate (PO), risedronate (PO), zoledronic acid (IV)
Denosumab: 1st line in prevention of hip, nonvertebral, vertebral # (Grade A)
YES fragility #: 18-24 mo duration, followed by long-term anti-resorptive therapy with bisphosphonate or RANKL inhibitor
Treatment Specific to Post-Menopausal Women
SERM (selective estrogen- receptor modulator): agonistic effect on bone but antagonistic effect on uterus and breast
HRT: combined estrogen + progesterone
(see Gynecology, GY34)
Raloxifene: 1st line in prevention of vertebral # (Grade A)
+ve: prevents osteoporotic # (Grade A to B evidence), improves lipid profile, decreased breast cancer risk
-ve: increased risk of DVT/PE, stroke mortality, hot flashes, leg cramps
1st line in prevention of hip, nonvertebral, and vertebral # (Grade A) For most women, risks > benefits
Combined estrogen/progestin prevents hip, vertebral, total # Increased risks of breast cancer, cardiovascular events, and DVT/PE