Bone mineral density (BMD) is known to fluctuate with age, hormonal profile, or presence of comorbidities. After reaching a peak, BMD gradually decreases with age, and osteopenia/osteoporosis are diagnosed when BMD decreases with over one/two and a half standard deviations below the adjusted mean values, respectively.

HIV infection associates a multitude of supplementary factors potentially accelerating the decrease of bone mineral density, i.e., the virus itself, the patient’s cytokine profile, antiretroviral treatment (ART), presence of multiple comorbidities, etc.^1,2

Bone evaluation in HIV positive patients is mandatory, particularly in those who acquired infection early in childhood, when bone turnover is high.^3,4 Data in field literature on the prevalence of osteopenia or osteoporosis in HIV infection are at best heterogeneous, and the studies performed are not comparable due to essential differences in the followed cohorts, i.e., duration of HIV infection, duration of ART, nadir CD4 cell count, race or gender.

To address this issue we have performed a literature review to gather data on BMD in HIV infection.

Review methodology

We searched PubMed for the following key terms: "HIV”, "osteopenia”, "osteoporosis”, "bone”, "BMD”. All identified studies relevant to this topic were included in the analysis. The following parameters were collected for each study: country and number of participants, prevalence of lumbar and femoral osteopenia and osteoporosis, mean or median age, mean or median duration of HIV infection, nadir CD4 cell count, and comments relevant to the study.

Literature review

The results of the literature review are summarized in the Table. Data from Romania are available for patients with a median duration of HIV infection of 9 years, and a median nadir CD4 cell count of 387 cells/cmm. 5 In this population lumbar osteopenia was diagnosed in 33.3% of patients and femoral osteopenia in 37.3%, while osteoporosis was identified in 13.7% (lumbar) and 7.8% (femoral). Data from Brazil in a similar cohort (9.9 years of HIV infection) reported a similar prevalence: 14.6% lumbar and 5.6% femoral osteoporosis.6 We were unable to identify data from a cohort similar in terms of nadir CD4 cell count. However, at lower nadir CD4 cell counts (i.e., 182 in Italy, 7 197 in Spain, 8 1789 and 18810 in the USA), the results are somewhat comparable for femoral osteoporosis: 10%7, 6%8 , and 10%, 9 with the exception of the low prevalence reported by Erlandson et al., 0.7%.10 Studies from the same country report different results for the prevalence of overall osteoporosis, ranging from 19.6%11 to 45%12 in Italy. The same thing applies to femoral osteopenia, with studies in the USA reporting values as low as 22.5%10 or 22.6%,13 and as high  as 51%9 , for the cohorts similar in terms of nadir CD4 cell count (i.e., 18810 vs. 1789 cells/cmm) but different in terms of duration of HIV infection (11.410 vs. 6.89 years). When looking at the median age of patients included in the studies performed in Romania (38 years)5 and the USA (41 years),9 we notice a slightly higher prevalence in the USA of femoral osteopenia (51%9 vs. 37.35 ) and femoral osteoporosis (10%9 vs. 7.8%5 ). However, in two other studies performed in the USA the reported prevalence was lower: 36% femoral osteopenia and 4% femoral osteoporosis in patients around 43 years of age14 and 22.6% and 1.6%, respectively, in patients around 39.2 years old.13 The results of two large international trials are also noteworthy. The first study reported results similar to those found in Romania, with a combined prevalence of lumbar and femoral osteopenia of 35.1% (notably, this trial also included patients from European countries such are Belgium, Ireland, Spain, UK).15 Their results were, however, completely different in terms of prevalence of osteoporosis, with numbers as low as 1.4% in the lumbar area and 0.5% in the  femoral area.15 The second international study was performed in the following countries: South Africa, India, Thailand, Malaysia, Argentina, and, except for the prevalence of lumbar osteopenia (31.3%), the reported numbers were much lower compared with the data from Romania (Table).  

Data reported in field literature regarding osteopenia and osteoporosis are extremelyheterogeneous in nature. This is in part due to the profound differences in the cohorts of patients, i.e., recently diagnosed patients vs. long-term survivors, but also due to the different definitions used for describing low BMD. When using the Z-score (for premenopausal women or males <50 years old), the International Society for ClinicalDensitometry (ISCD) defines low BMD for chronological age as Z-score ≤-2.0.16 When using the T-score (for postmenopausal women and men ≥50 years old), the World Health Organization (WHO) defines osteoporosis as T- score ≤-2.5 and osteoporosis as T-score between -2.5 and -1.0.17,18 Due to the different definitions employed in different studies, caution is warranted in interpreting and comparing data. Importantly, as clinicians we treat “the patient and not the disease” and therefore, regardless of national or international reports on prevalence of low BMD, each patient should undergo rigorous examination and screening procedures to identify any significant comorbidity and decide whether treatment is in order, based on the respective clinical significance of any changes in bone density. 

Data reported on the prevalence of osteopenia and osteoporosis in HIV-positive patients are extremely heterogeneous and cannot be reliably compared between different studies due to the different nature of the patient cohorts and the different definitions of low BMD used.

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