Bone studies at lipodystrophy workshop

9 December 2001. Related: Conference reports, Lipodystrophy Workshop (IWADRLH) 3rd Athens 2001.

Simon Collins, HIV i-Base

Several sessions at the meeting looked at complications related to bone, reporting higher rates in HIV-positive people than in age/sex matched general population.

The diversity of these changes, links to lipodystrophy and relationship to specific treatments will undoubtedly remain a growing concern; role of gender, exercise and diet should become integrated into future studies. Treatment for bone disorders was not covered at the meeting.

Mondy and colleagues reported on a range of bone histomorphometry identified from needle biopsies and biochemical markers of bone metabolism from nine HIV-positive men with evidence of primary osteopenia. [9]

Four patterns of changes were identified from the biopsy:

• Osteomalacia characterised by greatly increased osteoid volume (OV/BV), thickness (O Th) and surface area (OS/BS), increased mineralised lag time and diffuse irregular tetracycline labelling. Serum bone alkaline phosphotase and osteocalcin were also increased. (n=1)
• High bone turnover osteoporosis, characterised by increased osteoid volume, surface area and osteoblast content, increased bone turnover (increased mineralisation, formation and tetracycline labelling at all osteoid/mineralised bone interfaces.  Alkaline phosphotase was moderately increased. (n=1)
• Inactive osteoporosis, characterised by low osteoblasts and osteoclasts, decreased volume, thickness, surface area, bone formation rate and mineralising surface. (n=2)
• Osteoporosis with normal remodelling, relatively normal tetracycline labelling and indices of bone turnover.

The diversity of the forms of osteoporosis may imply different mechanisms behind the pathogenesis of bone changes in HIVinfection. The small numbers in the study did not show any correlation between ARV therapy and pattern of osteoporosis.

Rozenbaum and colleagues from Paris, looked at rates of osteoporosis and osteopenia in HIV-positive men (age 2555) treated with PI (n=47), NNRTI (n=23) or triple nucleoside(n=23) therapy for >18month, together with a group of untreated patients (n=25). BMD was measured by DEXA at femoral neck, trochanter and lumbar spine. [10]

Results identified frequency of osteoporosis at 711% and osteopenia at 4555% in the group as a whole, with no difference being reported (so presumably wasn’t detected) by treatment regimen. Lipodystrophy was present in 89% of PItreated and 74% of nonPI treatments compared to 4% of untreated group.

Falutz and colleagues from Quebec used DEXA scans to look at whether total body weight, fat mass (FM) and lean body mass (LBM) exerted an independent influence on bone mineral content (BMC) in 27 patients (24 male, 3 female). 15 people had typical features of lipodystrophy (LD). [11]

Trunk/extremity lean body mass was similar in LD+ and LD patients and trunk/extremity fat mass was higher in the LD+ group. No correlation was found between total fat or lean body mass and bone mineral content in either group. However associations were for the LD+ group between trunk FM and trunk BMC, arm LBM and arm BMC, and leg LBM and leg BMC (p=0.01, 0.02 and 0.005 respectively). No correlations were found for the LD group other that leg LBM and leg BMC (p=0.04).

Multiple regression analysis showed that FM and weight contributed significantly (23% and 20%) to total body BMC in LD+ patients, and that FM, LBM and height were contributory factors (25%, 23% and 31%) for those who were LD.

Madeddu and colleagues from Sassari, Italy, reported high rates of osteoporosis and osteopenia when comparing spine bone density (DEXA), serum osteocalcin, bone alkaline phosphatase between 148 HIV-positive patients (98 male, 50 female) to 55 agesex matched HIV-negative people. Of the HIV-positive group, 85 were on a PI-based combination.

Osteocalcin was significantly higher and bone alkaline phosphotase significantly lower in HIV-positive groups compared to controls. Additional differences between the PI and nonPI receiving HIV-positive groups included significantly higher osteocalcin, bone alkaline phosphotase, urinary pyridinium crosslinks in the PIreceiving group. Bone density and biochemical markers did not correlate with disease severity or treatment time. [12]

Mauss and colleagues from Dusseldorf assessed bone mineral density and metabolism in 24 asymptomatic patients (21 male, 3 female) who had HIV infection >10 years and ARV treatment >5 years and were not treated with corticosteroids or testosterone. [13]

Median characteristics included median age 48 years (3365), median duration of HIV infection 13 years (1019) and median time on ARV 6.5 years (511). Nearly all patients were multiple nucleoside, PI and NNRTI experienced. 12/24 patients were found to be osteopenic (compared to an expected 4/24 in an agematched population) although none had osteoporosis. Elevated markers of bone resorption were present in many of the osteopenic patients.

Finally, Lilienfield and colleagues searched 14,000 records from the MediCal (Medicaid California) database for reports of osteoporosis, aseptic osteonecrosis or hip fracture. [14] This BMS sponsored study reassuringly found no statistical difference between d4T and AZT use and the risk of these events (2.3 versus 2.9%, p>0.05) and that from this database at least, the risk is as great using either of these drugs.

References:

9. Mondy et al – Bone histomorphometry in HIVinfected men. Abstract 12. Antiviral Therapy 2001; 6 (Supplement 4):9
10. Rozenbaum et al – Osteoporosis and osteopenia in treated and nontreated HIV-positive patients. Abstract 32. Antiviral Therapy 2001; 6 (Supplement 4):25
11. Falutz et al – Influence of body composition on total body and regional bone mineral content in HIVinfected patients with or without the HIV/HAARTassociated lipodystrophy syndrome. Abstract 57. Antiviral Therapy 2001; 6 (Supplement 4):41
12. Madeddu et al – Bone mass loss risk in HIVinfected patients treated with HAART including PIs. Abstract 82. Antiviral Therapy 2001; 6 (Supplement 4):56.
13. Mauss et al – Assessment of bone mineral density and bone metabolism in long term HIVinfected adults with high ARV exposure. Abstract 85. Antiviral Therapy 2001; 6 (Supplement 4):58.
14. Lilienfeld et al Rate of osteoporosis/aseptic osteonecrosis/hip fracture is the same for users of d4T and AZT: a pharmacoepidemiologic investigation of 14000 HIV-positive persons in the MediCal population. Abstract 79. Antiviral Therapy 2001; 6 (Supplement 4):54.