Low Bone Mineral Density, Fracture Risk, and Kidney Dysfunction in HIV Positive Men

		SUMMARY: In a study that included mostly HIV positive men, 42% were found to have low bone mineral density (BMD) and 7% had evidence of kidney dysfunction, researchers reported in the December 1, 2009 Journal of Infectious Diseases. Use of tenofovir (Viread, also in the Truvada and Atripla combination pills) was linked to kidney impairment and increased bone turnover, but not to low BMD.

By Liz Highleyman

Several studies have assessed bone loss in people with HIV, but results have not been consistent. Most have shown that HIV positive people overall have decreased BMD, but it is still not clear whether this is attributable to HIV infection itself, antiretroviral therapy (ART), or both. Likewise, the role of proximal renal tubular dysfunction (PRTD) -- a type of kidney impairment -- and alterations in bone metabolism in this population are not fully understood.

Alexandra Calmy from St. Vincent's Hospital in Sydney, Australia, and colleagues measured BMD using dual-energy x-ray absorptiometry (DEXA), blood and urine markers of bone metabolism and kidney function, and risk factors for low BMD (hip or spine T score <-1). They then analyzed factors associated with low BMD and calculated 10-year fracture risk using the World Health Organization's FRAX equation.

The study included 153 adults in an ambulatory care setting. Almost all (98%) were men, the median age was 48 years, and the median body mass index was 24.5. Overall, participants had well controlled HIV disease, with a median CD4 count > 500 cells/mm3 and 83% having undetectable HIV RNA. With regard to ART, 44% were taking tenofovir and 53% were using boosted protease inhibitor-based regimens.

Results

	42% of study participants had low BMD, 16% had bone loss extensive enough to require bisphosphonate treatment, and 4% had osteoporosis (severe bone mineral depletion).
	7% of patients had proximal renal tubular dysfunction.
	Kidney dysfunction was significantly associated with longer duration of HIV infection, longer exposure to tenofovir, use of boosted protease inhibitors, and lower body mass index.
	In a multivariate analysis controlling for other factors, low BMD was linked to use of boosted protease inhibitors (odds ratio 2.69), while higher testosterone level was protective against bone loss.
	Use of tenofovir did not predict decreased BMD, but it was significantly associated with increased markers of osteoblast and osteoclast activity, indicating bone turnover (the process of absorption and rebuilding of bones).
	Mean estimated 10-year risks were 1.2% for hip fractures and 5.4% for any major fracture due to osteoporosis.

Based on these findings, the study authors concluded, "In this mostly male population, low BMD was significantly associated with protease inhibitor therapy."

"Tenofovir recipients showed evidence of increased bone turnover," they continued. "Measurement of BMD and estimation of fracture risk may be warranted in treated HIV-infected adults."

Given that participants mostly had well controlled HIV disease, undetectable viral load, and high CD4 cell counts, they suggested, "it is difficult to conclude that HIV replication and disease severity are important contributors to the observed low bone mineral density in our population."

HIV, Immunology and Infectious Diseases Unit and Centre for Applied Medical Research, St Vincent's Hospital, Garvan Institute for Medical Research, and National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia; HIV Unit, Geneva University Hospital, Geneva, and University Clinic for Infectious Diseases and University of Berne, Switzerland.

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Reference
A Calmy, CA Fux, R Norris, and others. Low bone mineral density, renal dysfunction, and fracture risk in HIV infection: a cross-sectional study. Journal of Infectious Diseases 200(11): 1746-1754 (Abstract). December 1, 2009.