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Low Bone Density Not Linked to Lipodystrophy in Small Group of Canadian Women (see report from Workshop below)
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1st International Workshop on HIV and Women, January 10-11, 2011, Washington, DC
from Jules: BUT here are numerous reports finding that being skinny, lipoatrophy & fat accumulation in the belly are associated with bone loss. In the general population it is well known being skinny is associated with bone loss. I think the point to take away from the Canadian study is that the study was conducted largely in Blacks suggesting a difference between whites and blacks in terms of bone loss, which we know that there are some difference.
Body Fat & Bone Loss: lipoatrophy & belly fat accumulation BOTH lead to bone loss - (09/25/10)
Racial differences in the relationship between vitamin D, bone ...
In adult participants of NHANES, the relationships between 25(OH)D, bone .... these investigators found no significant differences in BMD loss between ... blacks may require less dietary calcium than whites to maintain bone health [36]. ...
www.natap.org/2010/HIV/101610_01.htm
"In this cross-sectional analysis of relatively young adults in NHANES, BMD significantly decreased with declining 25(OH)D concentrations in whites and Mexican-Americans, but not in blacks.....Blacks are more efficient than whites in absorbing dietary sources of calcium, preserving calcium in the bones, and retaining calcium in the kidney, especially during adolescence [33-35], leading some to suggest that blacks may require less dietary calcium than whites to maintain bone health [36]. Accordingly, it is possible that blacks may also require a lower "set-point" for serum 25(OH)D to optimize calcium metabolism. Indeed, blacks maintain similar if not higher concentrations of 1,25-dihydroxyvitamin D than whites even at comparable concentrations of PTH [37-39], suggesting that blacks may be able to maintain adequate calcium homeostasis at lower circulating 25(OH)D levels than whites. In addition, it is possible that higher BMI among blacks may also contribute to racial differences in the relationships between 25(OH)D and BMD [40]."
Serum 25-Hydroxyvitamin D and Bone Mineral Density in a Racially ...
This could be problematic if our observations are driven by racial and ethnic differences in peak bone mass as opposed to rates of bone loss with aging. ...
www.natap.org/2008/HIV/012908_10.htm
"Black men had significantly higher BMD levels than Hispanic and White men at all BMD sites considered. BMD levels in Hispanic men were found to differ significantly from White men only at the femoral neck.....Racial and ethnic differences in vitamin D status and risk of osteoporosis are well documented. Among men, there is very strong evidence that Black men are at elevated risk of vitamin D deficiency (6, 7, 8, 9) but at lower risk of osteoporosis (10, 11), rapid bone loss (12), and associated fractures (13) compared with White men..... The purpose of this study was to provide descriptive data for three racial and ethnic groups of adult men living in a northeastern U.S. city (Boston, MA, latitude 42 degrees N) with respect to vitamin D status and BMD...."
Bone Loss in HIV+ Premenopausal Women & Fracture Risk
Rapid bone loss is defined as having more than a 3% decrease in BMD per year. ..... and Latina (women identifying as Hispanic but neither black nor white).
...www.natap.org/2010/HIV/020410_03.htm
Visceral Fat Causes Inflammation and Cytokines Leading To Bone Loss
Jan 15, 2010 ... Visceral Fat Causes Inflammation and Cytokines Leading To Bone Loss. Download the PDF here "Of importance, in our study, obese girls with ...
www.natap.org/2010/HIV/011610_01.htm
Bone Loss 62% in HIV+
Abdominal fat was determined by single slice CT-scan at L4. .... Initiation of ART Is Associated with Bone Loss Independent of the Specific ART Regimen. ...
www.natap.org/2007/CROI/croi_121.htm
"In multivariate analyses, low BMD was associated with older age, male gender, lower body mass index, unemployment, and stavudine use; osteoporosis was associated with older age, non-white race, lower body mass index, longer duration since HIV diagnosis, no resistance training, and unemployment (all p <0.05)."
"Potential confounding cofactors that can contribute to developing osteopenia include being sedentary, cigarette smoking, nutrition (including inadequate calcium intake), current or past steroid hormones (prior exposure to steroid treatment for PCP, use of Megesterol acetate for appetite stimulation, post-menopausal hormone deficiency), excessive alcohol intake, genetics, elevated lipids, possibly lower body mass, diseases such as kidney failure & thyroid overactivity, and long-term treatment with cortisone (but not anabolic steroids, which if anything increase BMD)."
Bone Mineral Density in HIV+ Women: Relationship to Body Composition
from Jules: actually, there have been previous reports associating lipoatrophy with bone loss, and this applies to men and women. ... www.natap.org/2009/CROI/croi_124.htm
"menopause was associated with a lower hip BMD. Disease duration negatively correlated with total hip BMD.....fat mass ratio negatively correlated with femoral neck BMD. Appendicular skeletal muscle mass index and CD4 lymphocytes nadir were the main determinant of BMD as they correlated with lumbar, total hip and femoral neck BMD......Sarcopenia (from the Greek meaning "poverty of flesh") is the degenerative loss of skeletal muscle mass and strength associated with aging.......20% of the patients had sarcopenia (appendicular skeletal muscle mass index <5.45 kg/m2) and 32% had lipodystrophy......Sarcopenia is characterized first by a decrease in the size of the muscle, which causes weakness and frailty.....Exercise and increases in activity have been shown to be beneficial in settings of sarcopenia; exercise even in the very old can increase strength and muscle function. Lack of exercise is currently thought to be a significant risk factor, increasing the likelihood of sarcopenia.[1]....The decline [in muscle] is precipitous after 65 years of age. A direct assessment of the effects of sarcopenia, even in extremely physically fit individuals, can be seen in the age-related decline in Masters athletics (track and field) world records of muscle-intensive sports, such as weight lifting......There is no generally accepted clinical test to diagnose sarcopenia. Primary management of sarcopenia is through the application of a graded exercise program, across both cardiovascular and strength domains, dosed in such a way as to provoke beneficial adaptation without overloading the weakened body.[3] Possible therapeutic strategies include resistance training and aerobic activity programs, as evidenced by recent studies. Nutritional evaluation may also be indicated if malnutrition is suspected, or current nutritional intake is insufficient to maintain adequate total body mass, although increased exercise also increases appetite. Physical activity incorporating resistance training is probably the most effective measure to prevent and treat sarcopenia."
Low Bone Density Not Linked to Lipodystrophy in Small Group of Canadian Women
1st International Workshop on HIV and Women, January 10-11, 2011, Washington, DC
Mark Mascolini
Although similar signaling pathways are involved in HIV lipodystrophy and low bone mineral density, Canadian researchers discerned no link between the two conditions in a small study of women with HIV [1].
Workers at Toronto's Maple Leaf Medical Clinic and Sunnybrook Health Sciences Centre planned this study because most BMD studies in people with HIV involve men and because possible links between low bone density and lipodystrophy remain poorly defined. Although estrogen helps protect premenopausal women from bone loss, the risk of osteopenia and osteoporosis jumps when women pass the menopause.
This cross-sectional study involved 47 HIV-positive women who were at least 18 years old, biologically female, and taking a stable antiretroviral regimen for at least 2 months. Everyone already had a DEXA scan to measure BMD. Study participants could not be pregnant.
These women completed a questionnaire that collected demographic data and ascertained the presence and degree of lipodystrophy. The Toronto investigators used HIV Outpatient Study criteria to diagnose lipodystrophy [2]; diagnosis requires (1) at least one severe symptom of fat redistribution OR (2) at least two symptoms of fat redistribution, one of which is at least moderate in severity. Fat redistribution is graded as 0 (absent), 1 (very mild), 2 (mild), 3 (moderate), or 4 (severe). Because the study group was relatively young, the researchers used a z-score definition of low bone mass, with a score below -2.5 indicating low BMD.
The investigators determined that 25 women (53%) had lipodystrophy. Women with lipodystrophy did not differ significantly from those without the syndrome in ethnicity, height, weight, body mass index, or age (medians of 42 with lipodystrophy and 39 without lipodystrophy, P = 0.42). Most study participants--18 with lipodystrophy and 15 without--were black. Women with lipodystrophy had a significantly wider waist circumference than the nonlipodystrophy group (96 versus 86.5 cm, P = 0.01).
The two groups did not differ in HIV transmission risk factors or proportions with an AIDS diagnosis or hepatitis virus coinfection. Duration of HIV infection was similar in the lipodystrophy group and the nonlipodystrophy group (7 versus 8 years), as was duration of antiretroviral therapy (3 versus 4 years), current CD4 count (500 versus 540), current viral load (below 50 copies), and use of a protease inhibitor or a nonnucleoside.
Average DEXA-determined z scores did not differ between women with and without lipodystrophy in the L1-L4 spine, femoral neck, or total hip. Average scores did not fall below -0.7 at any site in the lipodystrophy group or the comparison group. Univariate analysis found three factors associated with femoral neck BMD z score: older age (estimate per 10 years -0.063, 95% confidence interval [CI] -0.118 to -0.007, P = 0.03), black versus other race (estimate 0.155, 95% CI 0.070 to 0.240, P < 0.001), and menopause (estimate -0.163, 95% CI -0.301 to -0.024, P = 0.02). In a multivariate regression model, only black race remained associated with femoral neck BMD z score (estimate 0.133, 95% CI 0.036 to 0.231, P = 0.009). Lipodystrophy was not associated with femoral neck BMD in the univariate or multivariate analysis.
The researchers suggested the 70% prevalence of black race in their population may have skewed the race-related results. They proposed that reduced statistical power because of the small population size may have prevented detection of a correlation between lipodystrophy and reduced BMD. However, in 2008 a larger analysis of 359 men and 133 women in the French Aquitaine cohort found no independent correlation between lipodystrophy and low BMD in either men or women [3]. An earlier study of 51 HIV-positive men did find an association between increased abdominal visceral fat and low BMD [4]. The Canadian study may have suffered from combining fat atrophy and fat hypertrophy in the same analysis; FRAM famously determined that fat atrophy--but not fat hypertrophy--distinguishes people with HIV from the general population [5,6].
References
1. Hicks R, Luong M, Andany N, et al. Pilot study exploring the association between bone mineral density and lipodystrophy in HIV-positive women taking antiretroviral therapy. 1st International Workshop on HIV and Women. January 10-11, 2011. Washington, DC. Abstract O_15.
2. Lichtenstein KA, Ward DJ, Moorman AC, et al. Clinical assessment of HIV-associated lipodystrophy in an ambulatory population. AIDS. 2001;15:1389-1398.
3. Cazanave C, Dupon M, Lavignolle-Aurillac et al. Reduced bone mineral density in HIV-infected patients: prevalence and associated factors. AIDS. 2008;22:395-402.
4. Huang JS, Rietschel P, Hadigan CM, Rosenthal DI, Grinspoon S. Increased abdominal visceral fat is associated with reduced bone density in HIV-infected men with lipodystrophy. AIDS. 2001;15:975-982.
5. Bacchetti P, Gripshover B, Grunfeld C, et al. Fat distribution in men with HIV infection. J Acquir Immune Defic Syndr. 2005;40:121-131.
6. Study of Fat Redistribution and Metabolic Change in HIV Infection (FRAM). Fat distribution in women with HIV infection. J Acquir Immune Defic Syndr. 2006;42:562-571.
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