Elsevier

Joint Bone Spine

Volume 76, Issue 6, December 2009, Pages 637-641
Joint Bone Spine

Review
Bone loss in patients with HIV infection

https://doi.org/10.1016/j.jbspin.2009.10.003Get rights and content

Abstract

The prognosis of HIV infection has been considerably improved by the introduction of antiretroviral drugs. However, the longer survival times are associated with the emergence of new complications including decreased bone mineral density (BMD) values and/or bone insufficiency fractures. A meta-analysis of studies published between 1966 and 2005 showed bone absorptiometry results indicating osteoporosis in 15% of HIV patients and osteopenia in 52%. Longitudinal studies found no evidence that antiretroviral drug therapy contributed to the occurrence of bone loss. Available data indicate uncoupling with increases in bone resorption markers and decreases in bone formation markers. In addition to conventional risk factors for osteoporotic fractures, factors in HIV-infected patients may include malnutrition (wasting syndrome), hypogonadism, disorders in calcium and phosphate metabolism, and HIV infection per se. In patients with established bone insufficiency, bisphosphonate therapy should be considered. Alendronate in combination with vitamin D and calcium supplementation has been found effective in improving BMD values.

Introduction

In 2005, the French Institute for Public Health Surveillance estimated that 126,615 people were infected with the human immunodeficiency virus (HIV) nationwide. In the world, about 40 million people aged 15 to 49 years (1.2% of the population) are believed to be HIV-positive, and 4.8 million acquire the virus each year. Every day, 8500 people die of AIDS. In the mid-1990s, the introduction of antiretroviral drugs improved both the survival and the quality of life of HIV patients [1]. These drugs restore immune function and inhibit viral replication [2], [3].

Improved survival allows long-term complications to emerge. Thus, recent studies of long-term HIV survivors showed bone abnormalities such as decreased bone mineral density (BMD) values and changes in bone turnover markers. Many conflicting hypotheses have been put forward to explain these findings.

The HIV is a retrovirus, that is, an RNA virus whose replication requires two enzymes, a reverse transcriptase and a protease. Several available drugs used to treat HIV infection interfere with the effects of these enzymes, thereby inhibiting viral replication. Antiretroviral treatment consists of at least three antiretroviral drugs, usually two nucleoside reverse transcriptase inhibitors (nRTI) plus either a protease inhibitor or a nonnucleotide reverse transcriptase inhibitor (NNRTI). Less widely used regimens combine two protease inhibitors or more than three antiretroviral drugs. New drugs with different mechanisms of action were recently, or will soon be, introduced on the market. They include fusion inhibitors, integrase inhibitors, and CCR5 coreceptor inhibitors. The effects of these new drugs on bone are largely unknown.

The objective of this update is to supply general information on bone loss in HIV patients. Physicians who manage patients with HIV infection should be aware that effective treatments of established bone insufficiency are available. New longitudinal studies have clarified the role for antiretroviral drugs in the occurrence of bone loss.

Section snippets

Bone mineral density

Many studies of HIV patients showed low BMD values in the osteopenia or osteoporosis range. In a cross-sectional study of 148 HIV-positive men and 81 age-matched controls (mean age, 40 years), BMD values were significantly lower in the HIV patients both at the spine (T-score, −1.14 S.D. vs. −0.12 S.D., P = 0.001) and at the femoral neck (T-score, −1.03 S.D. vs. −0.36 S.D., P = 0.001). After adjustment for body mass index (BMI), smoking, and calcium intake, the difference remained significant (P = 

Bone histomorphometry

Few histomorphometric studies have been performed in HIV patients, and the results have been somewhat conflicting. In a study of 22 HIV patients (13 men and nine women with a median age of 27.9 years), histomorphometric studies of transiliac bone biopsies showed severe alterations in bone formation (bone formation rate/bone surface, 0.01 ± 0.01 vs. 0.04 ± 0.02 μm3/μm2/day in healthy controls, p = 0.05), bone turnover as assessed based on activation frequency (0.02 ± 0.03/year vs. 0.25 ± 0.13/year, P = 

Fracture risk in HIV patients

Two cases of osteoporotic fractures in men with HIV infection aged 49 and 51 years, respectively, were reported [25]. One had a rib fracture and the other a fracture of L1. Both were on antiretroviral treatment and had long-standing HIV infection [25]. Vertebral fractures occurred in two female African patients aged 29 and 31 years, respectively [26]. In a population-based cross-sectional study, 138 female HIV patients were compared to 402 female age-matched controls in Canada [27]. The

Risk factors for osteoporosis in HIV patients

In additional to the conventional risk factors clearly identified in studies of postmenopausal osteoporosis, low BMD values were associated in most studies with older age, weight loss, low BMI, smoking, and glucocorticoid therapy. Longer duration of HIV infection correlated with osteopenia in some studies [11], [12]. Lipodystrophy was not associated with low BMD [11], [12], [13]. Factors that may increase the risk of bone loss in HIV patients include malnutrition (wasting syndrome),

Pathophysiology of osteoporosis in HIV patients

The pathophysiological mechanisms underlying the bone metabolism disturbances seen in HIV patients are largely unknown. Several intertwined mechanisms are probably involved, such as direct effects of the HIV on bone cells, dysregulation of vitamin D metabolism, and elevated lactate levels. A role for disturbances in the metabolism of growth hormone and insulin-like growth factor has been suggested. The most appealing hypothesis, which is supported by a substantial body of data, involves chronic

Treatment of osteoporosis in HIV patients

Although the occurrence of fractures in HIV patients with low BMD values is well documented, efforts to detect and to treat, osteoporosis in this population remain inadequate. Of 55 HIV patients with a history of fracture, only 35% had received osteoporosis treatment, which usually consisted only in vitamin D and calcium supplementation, with only 10% receiving bone resorption inhibitors [33]. A systematic Cochrane review performed in 2007 identified three randomised controlled trials of

Conclusion

Bone metabolism disorders in HIV patients lead to low BMD values, changes in bone turnover markers, and histomorphometric abnormalities. In all likelihood, they increase the fracture risk. Nevertheless, whether routine assessment of the bone status in HIV patients is in order remains to be determined. A reasonable approach may be to focus on HIV patients with a history of insufficiency fracture or several risk factors for bone loss. In HIV patients with osteoporosis, bisphosphonate therapy

Conflicts of interest

The authors have no conflicts of interest to declare.

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