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  HIV DART 2008
Rio Grande, Puerto Rico
December 9-12, 2008
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Foot-Fractures in HIV+ Men
  HIV DART 2008, December 9-12, 2008, Rio Grande, Puerto Rico
Mark Mascolini
A retrospective case series from the Cedars-Sinai Health System in Los Angeles suggested a slightly higher risk of foot fracture among men taking tenofovir than among those not taking this antiretroviral [1]. Earlier research tied tenofovir to lower bone mineral density in adults and children [2-4]. But a bone substudy of the SMART treatment interruption trial did not isolate tenofovir as a risk factor for decreasing bone density [5]. In the Cedars-Sinai analysis, an array of contributing factors makes it impossible to discern the impact of tenofovir on foot fractures in these patients.
Collaborating with investigators from GlaxoSmithKline (the maker of competing products), the Cedars-Sinai team scrutinized medical records of all HIV-infected men in the Cedars-Sinai system with MRI-confirmed foot fractures. Among the 30 men with broken foot bones, 17 (57%) had taken a tenofovir-containing regimen before the fracture and 13 (43%) had not. Median time from starting tenofovir to foot fracture measured 2.57 years and ranged from 1.17 to 5.69 years. The tenofovir and nontenofovir groups were similar in several demographic and bone-related variables:
· Median age at fracture: 49 years with tenofovir, 48 years without tenofovir
· Median viral load: about 50 copies in both groups
· Median time between HIV diagnosis and foot fracture: 17 years in both groups
· Incidence of metatarsophalangeal fracture: 12% with tenofovir, 15% without tenofovir
· Incidence of vertebral fracture: 12% with tenofovir, 15% without tenofovir
· Family history of osteoporosis: 24% with tenofovir, 23% without tenofovir
· Concurrent use of bisphosphonates: 65% with tenofovir, 69% without tenofovir
· Concurrent use of calcitonin or diuretics similar in the two groups
· Frequency of malabsorption syndrome, renal failure, calcium deficiency, and vitamin D deficiency similar in the two groups
A higher proportion of tenofovir takers (35% versus 8%) smoked more than one pack of cigarettes daily, which may raise the risk of decreased bone mineral density. While 24% in the tenofovir group took prednisone, which also raises the risk of bone thinning, no one in the nontenofovir group used prednisone. On the other hand, the tenofovir group included a lower proportion of people whose records indicated alcoholism (12% versus 31%), which can damage bones. Rates of several other bone-related variables were higher in the tenofovir group, though it was not clear if their higher frequency reflected tenofovir use or was coincidental:
· Osteoporosis: 35% with tenofovir, 8% without tenofovir
· DEXA t score below 2.4 for femur: 24% with tenofovir, 9% without tenofovir
· DEXA t score below 2.4 for spine: 47% with tenofovir, 36% without tenofovir
· Stress-type fractures: 53% with tenofovir, 31% without tenofovir
· Other concurrent fractures: 12% with tenofovir, 0% without tenofovir
· Use of calcium supplements: 100% with tenofovir, 85% without tenofovir
· Use of vitamin D: 100% with tenofovir, 85% without tenofovir
· Use of testosterone: 47% with tenofovir, 23% without tenofovir
· Use of teriparatide (a bone-growth stimulant): 29% with tenofovir, 8% without tenofovir
· Concurrent protease inhibitor: 71% with tenofovir, 46% without tenofovir
· Concurrent nonnucleoside: 24% with tenofovir, 0% without tenofovir
· Wasting syndrome: 29% with tenofovir, 15% without tenofovir
· Central obesity: 18% with tenofovir, 8% without tenofovir
More people in the tenofovir group took lopinavir/ritonavir, which earlier research linked to greater bone loss than abacavir [6]. Logistic regression analysis did not identify tenofovir use as an independent predictor of foot fracture. This analysis found that a DEXA t score below 1.5 correlated with low weight (P = 0.036) and high serum glucose (P = 0.034).
A retrospective case series like this cannot implicate tenofovir as a cause of foot fracture. Only 4 more people with than without tenofovir experience broke a foot bone in this 30-man analysis, and potentially confounding variables cannot be sorted out. However, since most research of osteopenia and osteoporosis in HIV-infected people focuses on the hip and spine, the study should at least raise awareness of other potentially common fractures in people with HIV and encourage analysis of contributing factors.
1. Joseph R, Horizon A, Liao Q, Ross S, Pakes G. Foot fractures in HIV-infected patients previously treated with tenofovir (TDF)- versus non-TDF-containing highly active antiretroviral therapy. HIV DART 2008, December 9-12, 2008, Rio Grande, Puerto Rico. Abstract 5.
2. 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;49:298-308.
3. 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.
4. 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.
5. 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.
6. Rivas P, Gorgolas M, Garcia-Delgado R, et al. Evolution of bone mineral density in AIDS patients on treatment with zidovudine/lamivudine plus abacavir or lopinavir/ritonavir. HIV Med. 2008;9:89-95.