Osteoprotegerin and bone turnover markers in heavily pretreated HIV‐infected patients

Abstract

ObjectivesTo characterize osteoprotegerin (OPG) levels, bone remodelling and bone mineral density (BMD) in heavily pretreated HIV-infected patients on antiretroviral therapy, and to evaluate the clinical factors associated with bone density decline. MethodsHeavily pretreated (45 years) HIV-positive patients were enrolled in this cross-sectional, observational study, which was based on a total body bone densitometry examination and a comprehensive evaluation of bone and mineral parameters. ResultsSixty-eight patients (55 male and 13 female) with a median age of 41 years (range 25-60 years) were included in the study. Their antiretroviral treatment lasted for 82 months. On the basis of the World Health Organization criteria, nine patients (13.2%) were osteoporotic [T-scoreo À 2.5 standard deviation (SD)] and 19 patients (27.9%) were osteopenic (T-score between À 1 and À 2.5). The principal outcomes associated with the presence of a low BMD were high OPG and lysylpyridinoline/creatinine ratio ( There was an inverse correlation between T-scores and serum osteocalcin and alkaline phosphatase (AP) levels, on one hand, and Dpd, on the other. High AP and Dpd values were associated with relative risks of 4.1 [95% confidence interval (CI) 5 1.01-17.6] and 7.2 (95% CI 5 1.67-31.03), respectively, of a pathological T-score. Multivariate analysis revealed that the factors associated with the presence of osteopenia or osteoporosis were older age and lower body mass index. ConclusionsAbout 40% of our heavily pretreated subjects with advanced HIV infection had a low BMD, and 56% (24 of 44 patients) showed a high bone turnover rate with marked osteoclast activation. High OPG levels may protect against bone resorption.

Vitamin D deficiency in HIV-infected individuals: one more risk factor for bone loss and cardiovascular disease?

“…Similar results were reported in a US population of seropositive teenagers and young adults, employing a cut-off for serum 25(OH)D of 15 ng/mL, demonstrating a prevalence of 87% of hypovitaminosis D (12). Seminari, in Italy, found serum 25(OH)D levels of less than 18 ng/mL in 81,25% of the patients, aged 41 years, who were on ART and had been losing bone (24). Similar prevalence (86%) was described by Aparicio and cols.…”

“…Before antiretroviral treatment was introduced, few studies had indicated that bone metabolism was affected in HIVpositive patients, although it has recently been confirmed that infected patients present a higher risk of low bone mass and osteoporosis. Despite the fact that that was initially attributed to the use of these medications, it was later confirmed that its origins were due to a series of factors, one of the main ones being metabolic dysfunction of vitamin D (7,8,24).…”

Osteoarticular complications related to HIV infection and highly active antiretroviral therapy

“…The multiple factors listed as promoters of osteopenia include direct effects of the virus on osteogenic cells; persistent activation of proinflammatory cytokines, mainly TNF-α and interleukin-1; changes in vitamin D metabolism, with deficit of 1,25 di-hydrovitamin D, as well as the involvement of mitochondrial abnormalities related with lactic acidemia and the development of opportunistic diseases [4,5].…”

Calcification of the internal elastic lamina of coronary arteries

“…22 Each of these metabolic abnormalities is well documented in HIV-positive patients and may be due to HIV infection or to treatment with drugs such as protease inhibitors as part of highly active antiretroviral therapy (HAART). [23][24][25] In a recent meta-analysis, 15% of HIV-infected patients had osteoporosis, for a pooled odds ratio of 3.7 compared to HIV-negative controls. 26 In a separate study, vitamin D insufficiency (81%) and secondary hyperparathyroidism (26%) were other frequent findings among HIV patients treated with HAART for more than 5 years.…”

“…26 In a separate study, vitamin D insufficiency (81%) and secondary hyperparathyroidism (26%) were other frequent findings among HIV patients treated with HAART for more than 5 years. 25 Osteoporosis, hyperparathyroidism, elevated calcium phosphate product, chronic renal failure, and diabetes mellitus have all been associated with medial as well as intimal calcification. 2,22,27,28 Although we have little evidence of patients in this study suffering from these conditions, many were HIV-infected and heavily exposed to HAART.…”