DETERMINANTS OF SKELETAL HEALTH IN AFRO-CARIBBEAN MEN

Osteoporosis is a common senile condition with major public health impact in both genders of all races. Very little is known about the natural history and etiology of bone loss, and trabecular and cortical volumetric bone mineral density (vBMD) in men, especially in men of African heritage.This research project was to evaluate age-related patterns and potential correlates for the rate of decline in areal BMD (aBMD) at the proximal femur, and vBMD at the radius and tibia in a cohort of Afro-Caribbean men aged 40 and above from the Tobago Bone Health Study. We also investigated the genetic associations of variants in a gene involved in the bone mineralization process, ectonucleotide pyrophosphatase/ phosphodiesterase 1 (ENPP1), with bone loss, aBMD and vBMD. In longitudinal analyses, a significantly greater rate of bone loss was observed in men aged 40-45 than those aged 45-49 and 50-54. Thereafter, the rate of bone loss accelerated with advancing age. The rate of bone loss was also comparable with those observed in Caucasian men. Additionally, we identified low body mass index, weight loss, prostate cancer, and treatment for prostate cancer with androgen deprivation (ADT) as potential determinants for accelerated bone loss.In cross-sectional analyses of vBMD, we observed an early decline of trabecular vBMD before age 50 and with a slower decline thereafter into 7th decade. Cortical vMBD, however, appeared to decrease with advancing age in a linear fashion. Correlates of vBMD included weight, diabetes, prostate cancer, ADT, cigarette smoking and bone chewing.In genetic association study, several variants in the ENPP1 gene were strongly associated with bone loss, aBMD or vBMD. More associations were found with cortical vBMD than with the other phenotypes.Our findings have important public health relevance as they increase our understanding of vBMD and age-related bone loss in an under-studied population. We have also identified a novel association of ENPP1 gene variants with bone loss and BMD in this population of African heritage. Additional research is needed to better understand the factors related to BMD and bone loss in populations of African ancestry, especially the apparent early loss of bone mass

Vertebral bone marrow fat, bone mineral density and diabetes : The Osteoporotic Fractures in Men (MrOS) study

Elevated vertebral bone marrow fat (BMF) among individuals with osteoporosis has been established in histomorphometric studies. Several studies have found a negative correlation between BMF and bone mineral density (BMD) at the spine in men and women across different age groups. Animal studies have also observed bone loss with increased BMF in mice with induced diabetes. Our study objective was to test the hypothesis that the association between BMF and BMD varies by diabetic status. We performed a cross-sectional study of 156 men aged 74-96years from the Osteoporotic Fractures in Men study at the Pittsburgh clinical site. All men had spine BMF scans using proton magnetic resonance spectroscopy and spine and hip BMD scans by dual-energy X-ray absorptiometry. BMF was expressed as lipid to "lipid+water" ratio (%). Men were considered diabetic if they self-reported a physician diagnosis of diabetes, diabetes medication or had a fasting glucose ≥126mg/dl. Men with diabetes (n=38) had a significantly higher spine BMF (58.9 vs. 54.6%, p=0.0035), spine BMD (1.20 vs. 1.10g/cm(2), P=0.007) and total hip BMD (1.00 vs. 0.94g/cm(2), p=0.04) than those without, while no differences were observed for body weight, body mass index or waist circumference. Pearson correlation tests showed no significant correlation of spine BMF with age or BMD in non-diabetics. Significant inverse correlations were observed between BMF and BMD (-0.30 for femoral neck and -0.39 for total hip) among diabetic men. In conclusion, men with diabetes had a higher BMF compared to non-diabetic men. The correlation between BMF and BMD differed by diabetes status. Further investigation of the association of diabetes with BMF and BMD may provide a better understanding of the high fracture rates among individuals with diabetes despite their higher BMD

Natural History and Correlates of Hip BMD Loss With Aging in Men of African Ancestry: The Tobago Bone Health Study

Little is known about the magnitude, pattern, and determinants of bone loss with advancing age among men, particularly among those of African descent. We examined the rate of decline in hip BMD and identified factors associated with BMD loss among 1478 Afro-Caribbean men ≥40 yr of age. BMD was measured at baseline and after an average of 4.4 yr by DXA. The rate of decline in femoral neck BMD was 0.29 ± 0.81%/yr in the total sample (p < 0.0001). However, a U-shaped relationship between advancing age and the rate of decline in BMD was observed. The rate of decline in BMD at the femoral neck was −0.38 ± 0.77%/yr among men 40–44 yr of age, decelerated to −0.15 ± 0.81%/yr among men 50–54 yr of age, and then accelerated to −0.52 ± 0.90%/yr among those 75+ yr of age (all p < 0.003). Men who lost ≥5% of their body weight during follow-up had significantly greater BMD loss than those who remained weight stable or gained weight (p < 0.0001). The relationship between weight loss and BMD loss was more pronounced among men who were older and leaner at study entry (p < 0.03). We also observed a strong impact of advanced prostate cancer and its treatment with androgen deprivation on BMD loss. Men of African ancestry experience substantial BMD loss with advancing age that seems to be comparable to the rate of loss among white men in other studies. Additional studies are needed to better define the natural history and factors underlying bone loss with aging in men of African ancestry

Vertebral bone marrow fat, bone mineral density and diabetes: The Osteoporotic Fractures in Men (MrOS) study

Elevated vertebral bone marrow fat (BMF) among individuals with osteoporosis has been established in histomorphometric studies. Several studies have found a negative correlation between BMF and bone mineral density (BMD) at the spine in men and women across different age groups. Animal studies have also observed bone loss with increased BMF in mice with induced diabetes. Our study objective was to test the hypothesis that the association between BMF and BMD varies by diabetic status. We performed a cross-sectional study of 156 men aged 74-96years from the Osteoporotic Fractures in Men study at the Pittsburgh clinical site. All men had spine BMF scans using proton magnetic resonance spectroscopy and spine and hip BMD scans by dual-energy X-ray absorptiometry. BMF was expressed as lipid to "lipid+water" ratio (%). Men were considered diabetic if they self-reported a physician diagnosis of diabetes, diabetes medication or had a fasting glucose ≥126mg/dl. Men with diabetes (n=38) had a significantly higher spine BMF (58.9 vs. 54.6%, p=0.0035), spine BMD (1.20 vs. 1.10g/cm2, P=0.007) and total hip BMD (1.00 vs. 0.94g/cm2, p=0.04) than those without, while no differences were observed for body weight, body mass index or waist circumference. Pearson correlation tests showed no significant correlation of spine BMF with age or BMD in non-diabetics. Significant inverse correlations were observed between BMF and BMD (-0.30 for femoral neck and -0.39 for total hip) among diabetic men. In conclusion, men with diabetes had a higher BMF compared to non-diabetic men. The correlation between BMF and BMD differed by diabetes status. Further investigation of the association of diabetes with BMF and BMD may provide a better understanding of the high fracture rates among individuals with diabetes despite their higher BMD

Greater Adipose Tissue Infiltration in Skeletal Muscle among Older Men of African Ancestry

Context: There is substantial variability across ethnic groups in the predisposition to obesity and associated metabolic abnormalities. Skeletal muscle fat has been identified as an important depot that increases with aging and may contribute to the development of diabetes