Different impact of NNRTI and PI-including HAART on bone mineral density loss in HIV-infected patients

OBJECTIVE: To evaluate the changes in Bone Mineral Density (BMD) and bone
remodelling markers in a group of HIV patients treated with HAART and controlled
in a long follow-up and to identify possible risk factors for accelerated bone
mass loss.
PATIENTS AND METHODS: In a series of 172 HIV patients treated with HAART a total
of 67 patients (44 males and 33 females) underwent repeated bone mineral density
measurement by DEXA in lumbar spine and in femur; the patients were classified
according to T-score WHO criteria. Serum bone alkaline phosphatase (BAP), by
IRMA, and urine pyridinoline/deoxypyridinoline (PYD&DPD), by EIA, were also
assayed in all cases.
RESULTS: At baseline, 62/67 patients were on HAART, while 5 were naïve; 44.8%
were previous intravenous drug users (IVDU), 46.3% heterosexual and 8.9%
homosexual, mean age being 40.2 ± 6.5 years, and 23.9% had previous AIDS
diagnosis. Fifteen/67 (22.4%) of treated patients had osteoporosis and 25/67
(37.3%) osteopenia in spine and/or femur including 3 naïve, 27/67 (40.3%),
including 2 naïve, had normal BMD in both sites. Fifty-one/67 patients were
monitored during follow-up (56.8 ± 5.3 months); 27 (52.9%) of these (Group 1),
received protease inhibitors (PI) and 24 (47.1%), including naïve, (Group 2)
received not nucleoside reverse transcriptase inhibitors (NNRTI) for > 50% of
follow-up period. In Group 1 patients, BMD reduction was observed after follow-up
in respect of basal condition in both spine and femur, but significantly (p =
0.011) only for the latter. However, mean BMD values remained stable in both
sites in Group 2 patients. Basal BAP and PYD&DPD levels were higher in Group 1
than Group 2, but not significantly. Moreover, only PYD&DPD levels at the
follow-up evaluation were significantly (p = 0.031) higher in Group 1 than Group
2. Of the remaining 16/67 patients with osteoporosis/osteopenia, 10 received PI
and 6 NNRTI and were treated with therapies that could increase bone density, in
particular, 9 with Alendronate/Vitamin D/Calcium and 7 with only vitamin
D/calcium; these patients were excluded from statistical analysis of 51 Group
1/Group 2 cases. In the 16 patients, after these specific treatments, mean spine
and femur BMD increased over time, but significantly only in those cases
including alendronate in their protocol.
CONCLUSIONS: The study showed that in HIV patients on HAART BMD decrease, even
osteoporosis, can be present persisting over time, particularly in PI in respect
of NNRTI treated patients. The pathogenesis is probably multifactorial, the
different antiviral drugs seeming to differently affect bone metabolism.
Alendronate/Vitamin D/Calcium therapy can be useful to slow down bone mass loss
and also improve osteoporosis/osteopenia conditions, thus, reducing fracture risk
also continuing HAART.