Challenges in the Management of Osteoporosis and Vitamin D Deficiency in the HIV-Infected Patient

1. Challenges in the Management of Osteoporosis and Vitamin D Deficiency in the HIV-Infected Patient Todd T. Brown, MD, PhDAssociate Professor of Medicineand EpidemiologyThe Johns Hopkins UniversitySchool of MedicineAtlanta, GA From TT Brown, MD, at Atlanta, GA: April 10, 2013, IAS-USA.

2. Pathophysiology and Risk Factors HIV Disease Factors Inflammation and Viral Proteins ↑ bone resorption ↓ bone formation Medication Factors Tenofovir Certain PIs (ATV/r) ART initiation (↓ 2-6% over 96 weeks)

3. Pathophysiology and Risk Factors Patient-Related Factors Low Body Weight Smoking Alcohol Use Opiate Use Hepatitis C Co-infection Physical Inactivity Hypogonadism Low Vitamin D

4. “we recommend a DXA scan for all HIV-infected post-menopausal women and men >50 years” CID, October 2010

5. Definitions Functional Definition (DXA)- WHO Definition Osteoporosis: T-score < -2.5 Osteopenia: T-score= -1.0 to -2.5 Normal: T-score > -1.0 ↑ Risk of fracture by 1.5-3.0 x for each SD decrease Caveats: Z-score (<-2.0) used in men < 50 years and premenopausal women BMD explains only about 50% of fracture risk

6. 2008 US NOF Guidelines: Who to Treat* Those with hip or vertebral fractures Those with BMD T-scores ≤ -2.5 at the femoral neck, total hip, or spine by DXA Those with T-score b/t -1 and -2.5 (osteopenia) at above sites AND 10-year hip fracture probability ≥ 3% or 10-year all major osteoporosis-related fracture ≥ 20% based on FRAX model *applies to post-menopausal women and men ≥ 50 years

7. Secondary Causes of Low BMD • Vitamin D deficiency 25 OH Vit D • Hyperparathyroidism PTH, Ca++ • Subclinical Hyperthyroidism TSH • Hypogonadism Males: Free Testosterone • Phosphate wasting Fractional Excretion of Phosphate • Idiopathic Hypercalciuria 24 hr Urinary Calcium • Celiac Sprue Tissue Transglutaminase • Multiple Myeloma Serum Protein Electrophoresis • Mastocytosis  Serum Tryptase • Cushing’s Syndrome  24 hr Urinary Free Cortisol

8. Dealing with Vitamin D: My Strategy • If BMD is low or history of falls, check 25OHD: • >30 ng/mL: 1000 IU/d • 20-30 ng/mL: 2000 IU/d • 15-20 ng/mL: Ergocalciferol 50K units weekly x 8 weeks, then D3 2000 IU/d • <15 ng/mL: Ergocalciferol 50K units once or twice a week x 8-12 weeks, then D3 2000 IU/d, recheck 25OHD after ergo course • More aggressive replacement if PTH is high or s/s of osteomalacia

9. Management Options • General recommendations • Calcium/vitamin D supplementation • Smoking cessation, alcohol reduction • Weight-bearing exercise • Assess fall risk (Are you worried about falling?) • Strength/balance training • Rx options • Bisphosphonates • Selective estrogen receptor modulator • Estrogen • PTH analogue

10. Conclusions DXA screening recommended in HIV-infected patients in men > 50 yrs and post-menopausal women Treatment guidelines should follow those established for the general population Remember secondary causes (vit D def and phosphate wasting) Use absolute risk of fracture to help guide decision making