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Low Vitamin D Tied to High Bone Marker Levels in Men Taking Tenofovir
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48th ICAAC, October 25-28, 2008, Washington, DC
Mark Mascolini
Men taking tenofovir (TDF) had higher levels of parathyroid hormone (PTH), a signal of abnormal calcium metabolism, than antiretroviral-treated men not taking TDF in a small cross-sectional study [1]. Parathyroid hormone concentrations were particularly high in TDF-treated men with low vitamin D, measured as 25(OH)D. Although these findings must be seen as preliminary, the researchers believe the results suggest that "adequate doses of vitamin D supplements along with TDF may prevent secondary hyperparathyroidism, a serious condition linked to bone loss and cardiovascular disease." But they cautioned that this tactic requires validation in a clinical trial.
This cross-sectional study relied on record reviews and interviews with 51 antiretroviral-treated men in New York City, 34 of them taking a TDF/emtricitabine (FTC) regimen and 17 not taking TDF. All men had a glomerular filtration rate above 60, indicating good kidney function, and all had normal serum calcium. Median CD4 count stood at 443 (interquartile range 290 to 698) in the whole study group, and 75% of men had an undetectable viral load. Researchers at the Mount Sinai School of Medicine used the Immulite 2000 assay to measure PTH, setting 65 pg/mL as the upper limit of normal.
Men taking TDF did not differ significantly from the no-TDF group in age, body mass index, years of HIV infection, CD4 count, proportion with undetectable HIV load, or glomerular filtration rate. PTH was above normal in 13 men TDF (39%) taking versus 1 (7%) of those not taking TDF (P = 0.036). Median plasma PTH measured 80 pg/mL in the TDF group and 55 pg/mL in the no-TDF group (P = 0.02). No one with optimal 25(OH)D levels had elevated PTH.
Looking only at men taking TDF, the Mount Sinai team charted significantly higher PTH levels in those with a vitamin D level below 30 ng/mL than in those with more vitamin D (P = 0.045). Among men with a vitamin D reading below 30 ng/mL, PTH levels were significantly higher in people taking TDF than in those not taking TDF (P = 0.021). Multivariate analyses not detailed in the study poster indicated that abnormal 25(OH)D and TDF/FTC therapy were independently associated with plasma PTH (P = 0.03 for 25(OH)D and P = 0.04 for TDF/FTC). Serum creatinine did not correlate with plasma PTH in this analysis.
The investigators suggested that TDF may be associated with secondary hyperparathyroidism in men with low vitamin D, but not necessarily in those with adequate vitamin D concentrations. Although PTH is a marker of bone metabolism, this study did not assess bone density in these men. A scan of the medical literature turned up 1 case report of secondary hyperparathyroidism in a TDF-treated patient with Fanconi syndrome [2].
The investigators called for research to determine whether prophylactic vitamin D3 supplements plus calcium citrate will prevent PTH elevations and preserve bone in people taking TDF. It would also be helpful to duplicate these findings in a larger group. Conducting such a study over time, rather than in a cross-sectional slice of time, would give a clearer picture of how ongoing TDF therapy may affect PTH levels. Several studies link TDF therapy to waning bone mineral density in adults and children [3-6], but a SMART trial substudy at this meeting (reported separately by NATAP) saw no link between TDF and falling bone density [7].
References
1. Childs K, Fishman S, Bateman K, et al. Should vitamin D be prescribed with tenofovir/FTC? 48th Annual International Conference on Antimicrobial Agents and Chemotherapy (ICAAC). October 25-28, 2008. Washington, DC. Abstract H-2300.
2. Torres Isidro MV, García Benayas T, del Val Gomez Martinez M, et al. [Role of bone gammagraphy in the diagnosis of secondary osteomalacia in a patient treated with tenofovir] [Article in Spanish]. Rev Esp Med Nucl. 2006;25:103-106.
3. Jacobson DL, Spiegelman D, Knox TK, Wilson IB. Evolution and predictors of change in total bone mineral density over time in HIV-infected men and women in the Nutrition for Healthy Living Study. J Acquir Immune Defic Syndr. 2008 Oct 3. Epub ahead of print.
4. Purdy JB, Gafni RI, Reynolds JC, Zeichner S, Hazra R. Decreased bone mineral density with off-label use of tenofovir in children and adolescents infected with human immunodeficiency virus. J Pediatr. 2008;152:582-584.
5. Jones S, Restrepo D, Kasowitz A, et al. Risk factors for decreased bone density and effects of HIV on bone in the elderly. Osteoporos Int. 2008;19:913-918.
6. The Strategies for Management of Antiretroviral Therapy (SMART) Study Group. CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med. 2006;355:2283-2296.
7. Grund B, Carr A. Continuous antiretroviral therapy (ART) decreases bone mineral density: results from the SMART study. 48th Annual International Conference on Antimicrobial Agents and Chemotherapy (ICAAC). October 25-28, 2008. Washington, DC. Abstract H-2312a.
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