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A growing body of research indicates that people with HIV are at higher risk for bone problems compared with the general population, including reduced bone mineral density (osteopenia) and more advanced bone loss known as osteoporosis. Low bone density can increase the risk of fractures.

Anna Bonjoch from Lluita SIDA Foundation and colleagues aimed to determine the prevalence of and predictive factors associated with low bone mineral density (BMD) and bone loss as measured by dual energy X-ray absorptiometry (DEXA).

Bone loss is caused mainly by "lifestyle factors" such as smoking, alcohol intake or malnutrition, the researchers noted as background in a press release issued by ICAAC. However, the presence of other disease (e.g., hormone deficiency, vitamin D deficiency, or thyroid problems) or some medical therapies (e.g., prolonged use of corticosteroids or antiepileptic agents) may also play a role. HIV infection itself, resulting inflammation, antiretroviral therapy, or some combination may also increase the risk.

This retrospective analysis included 391 HIV positive individuals at a Barcelona clinic (out of a total patient population of about 2300) who received at least 2 DEXA scans (median 3) between 2000 and 2009. Measurements were separated by 2.5 years on average, and by more than 5 years for 27% of participants.

About three-quarters of participants were men, the median age was 43 years. Almost all were on ART, with an average duration of 8 years; about half were taking protease inhibitors and about half were on tenofovir (Viread, also in the Truvada and Atripla coformulations), which has been linked to bone problems in some studies.

 

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Results

 

• 49% of first DEXA scans and 50% of final scans showed osteopenia.
• 22% and 27%, respectively, met the diagnostic criteria for osteoporosis.
• 28% of patients progressed from their first to last DEXA:

o      13% progressed from normal BMD to osteopenia;

o      16% progressed from osteopenia to osteoporosis.

• Among participants with more than 5 years of follow-up, bone loss progression rates were higher:

o      18% progressed to osteopenia;

o      29% progressed to osteoporosis.

• In a multivariate analysis, factors significantly related to bone loss progression were:

o      Older age: odds ratio (OR) 1.07 per year, or 7% increase;

o      Male sex: OR 2.2, or about twice the risk;

o      Low body mass index (BMI): OR 0.87;

o      More time on tenofovir: OR 1.08 per year, or 8% increase;

o      More time on protease inhibitors: OR 1.18 per year, or 18% increase;

o      However, being on a protease inhibitor at the time of DEXA scans was associated with decreased risk: OR 0.61.

"Prevalence of low BMD was high in our cohort, 28% of patients progressed to osteopenia or osteoporosis during a mean follow-up of 2.5 years," the investigators concluded.

Some risk factors associated with low BMD were similar to those described for the general population, including older age, sex, and low BMI, they added, while others were related to antiretroviral treatment and specifically protease inhibitor and tenofovir use.

"Both findings suggest the necessity of monitoring BMD in this population," they recommended.

"These results demonstrate the high frequency of these abnormalities and the need for an early detection and prevention of them," Bonjoch said.

Vitamin D

Two research teams presented data showing that low vitamin D levels were common among people with HIV.

In the first study (abstract H-225), Armelle Pasquet and colleagues from the University Hospital Center of Lille evaluated the prevalence of and risk factors for 25-hydroxy-vitamin D deficiency among 395 French patients in the Tourcoing HIV clinical cohort between January 2008 and January 2009. Nearly 70% were men and the median age was 45 years. Most (89%) were on ART and the median CD4 cell count was high at 575 cells/mm3.

Vitamin D levels were categorized as normal (>30 ng/mL), moderate deficiency (10 to 30 ng/mL), or severe deficiency (<10 ng/mL). The median level was 15 ng/mL, at the low end of the moderate range. Overall, 90% had some degree of vitamin D deficiency, with 58% having moderate and 32% having severe deficiency. A total of 41% fell below the median level.

Age, sex, BMI, CD4 cell count, and time since HIV diagnosis were not significantly associated with moderate or severe deficiency. However, people with severe deficiency had used protease inhibitors for a shorter time (34, 51, and 45 months, respectively, for patients with severe, moderate, and no deficiency). There was also a trend toward lower vitamin D levels among NNRTI users, but this did not reach statistical significance for any specific drug.

In the second study (abstract H-225), Miguel Cervero from Hospital Severo Ochoa in Madrid likewise examined the prevalence and causal factors for vitamin D deficiency among HIV positive patients, and in particular whether antiretroviral drugs might interfere with vitamin D metabolism.

This cross-sectional analysis included 147 HIV positive outpatients followed from January 2008 through January 2010. Nearly 70% were men and about 90% were white. Again, most were on ART and a majority had suppressed viral load. In addition to various blood measurements including calcium, phosphate, and parathyroid hormone, a nutritionist monitored vitamin D dietary intake and sun exposure, as sun enables the body to manufacture its own vitamin D (with lighter skinned people making more).

In this study, the median serum 25-hydroxy-vitamin D level was 21 ng/mL. Nearly three-quarters had less than 30 ng/mL and about half had less than 20 ng/mL (defined here as deficiency). In a multivariate analysis, people tested during in the spring -- that is, after a period of reduced sun exposure -- were significantly more likely to be deficient than those tested in the fall. Interestingly, people in the heterosexual HIV transmission risk group (compared with injection drug users) and those with higher BMI also had an unexplained greater likelihood of deficiency. Use of nevirapine (Viramune) was associated with a significantly lower risk. Race was not a risk factor in this analysis, but blacks were underrepresented.

"Despite the low latitude and high number of sunny days of Spain, moderate vitamin D deficiency in HIV-infected patients is more prevalent in our cohort than in the cohorts of Switzerland, Netherlands and Boston, in which there should be a lower level of exposure to sunlight," the researchers noted in an ICAAC press release.

"Since low vitamin D has been related to increased risk of infections, of several malignancies, and with higher cardiovascular risk, studies should be carried out to analyze the impact of vitamin D on the increase of CD4 counts, and on the reduction of cardiovascular episodes, infectious complications, and malignant neoplasias in HIV-infected population[s]," they added.

Investigator affiliations: Abstract H-226: Lluita SIDA Foundation, Badalona, Spain; Statistics and Operations Res., Technical Univ. of Catalunya, Barcelona, Spain; Irsicaixa Foundation, Badalona, Spain. Abstract H-225: Hosp. Dron, Tourcoing, France; CHRU, Lille, France.
Abstract H-230: Hosp. Severo Ochoa, Madrid, Spain.

10/15/10

References

A Bonjoch, M Figueras, J Puig, and others. Bone Mineral Density in a Large Cohort of HIV Infected Patients. 50th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2010). Boston, September 12-15, 2010. Abstract H-226.

A Pasquet, N Viget, P. Choisy, and others. Prevalence and Risk Factors for Hypovitaminosis D among HIV-Infected Patients in a French HIV Clinical Cohort. ICAAC 2010. Abstract 225.

M Cervero, V Alcazar, C Garcia-La Calle, and others. Prevalence of Vitamin D Deficiency in HIV infection. ICAAC 2010. Abstract H-230.

Other Sources

ICAAC. Frequency of osteoporosis in HIV population. Press release. September 12, 2010.

ICAAC. Percentage of HIV-infected patients with low levels of vitamin D. Press release. September 12, 2010.