Aromatase activity and bone loss in men.
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ABSTRACT:
SUBMITTER: Merlotti D
PROVIDER: S-EPMC3135090 | biostudies-literature | 2011
REPOSITORIES: biostudies-literature
Publications
Aromatase activity and bone loss in men.
Merlotti Daniela D Gennari Luigi L Stolakis Konstantinos K Nuti Ranuccio R
Journal of osteoporosis 20110624
Aromatase is a specific component of the cytochrome P450 enzyme system responsible for the transformation of androgen precursors into estrogens. This enzyme is encoded by the CYP19A1 gene located at chromosome 15q21.2, that is, expressed in ovary and testis, but also in many extraglandular sites such as the placenta, brain, adipose tissue, and bone. The activity of aromatase regulates the concentrations of estrogens with endocrine, paracrine, and autocrine effects on target issues including bone ...[more]
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Project description:Accelerated bone loss (ABL) shown on routine dual-energy X-ray absorptiometry (DXA) may be accompanied by microarchitectural changes, increased cortical porosity, and lower bone strength. To test this hypothesis, we performed a cross-sectional study and used high-resolution peripheral quantitative computed tomography (HR-pQCT) scans (Scanco Medical AG, Brüttisellen, Switzerland) to measure estimated bone strength and microarchitecture in the distal radius and distal and diaphyseal tibia. We studied 1628 men who attended the year 14 exam of the Osteoporotic Fractures in Men (MrOS) study. We retrospectively characterized areal bone mineral density (aBMD) change from the year 7 to year 14 exam in three categories: "accelerated" loss, ?10% loss at either the total hip or femoral neck (n?=?299, 18.4%); "expected" loss, <10% (n?=?1061, 65.2%), and "maintained" BMD, ?0% (n?=?268, 16.5%). The ABL cut-off was a safety alert established for MrOS. We used regression models to calculate adjusted mean HR-pQCT parameters in men with ABL, expected loss, or maintained BMD. Men who experienced ABL were older and had a lower body mass index and aBMD and experienced greater weight loss compared with other men. Total volumetric BMD and trabecular and cortical volumetric BMD were lower in men with ABL compared with the expected or maintained group. Men with ABL had significantly lower trabecular bone volume fraction (BV/TV), fewer trabeculae, and greater trabecular separation at both the distal radius and tibia than men with expected loss or who maintained aBMD, all p trend <0.001. Men with ABL had lower cortical thickness and lower estimated bone strength, but there was no difference in cortical porosity except at the tibia diaphyseal site. In summary, men with ABL have lower estimated bone strength, poorer trabecular microarchitecture, and thinner cortices than men without ABL but have similar cortical porosity. These impairments may lead to an increased risk of fracture. © 2018 American Society for Bone and Mineral Research.
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Project description:Background:Disrupted rest-activity circadian rhythm (RAR) patterns have been associated with poor health outcomes (i.e. diminished cognitive function, increased risk of dementia and falls). Circadian time cues in bone influence the differentiation of osteoblasts and osteoclasts, and bone turnover markers exhibit circadian variation; relationships between bone outcomes and RAR are emerging areas of research. We evaluated associations between RAR and areal bone mineral density (aBMD) at the total hip and femoral neck in older men from the Osteoporotic Fractures in Men (MrOS) cohort. We hypothesized that weaker RAR patterns would be associated with lower aBMD. Methods:MrOS is an ongoing prospective cohort study following ambulatory men ? 65 years (n = 5994) at 6 U.S. clinics (baseline enrollment 3/2000-4/2002); participants for this analysis are from an ancillary study, Outcomes of Sleep Disorders in Older Men (MrOS Sleep). We included data from men who had technically adequate measures of RAR and aBMD at Sleep Visit 1 (12/2003-3/2005), with repeat aBMD at core Visit 3 (3/2007-3/2009) (n = 2412; mean age at Sleep Visit 1: 75.7 ± 5.2 years). aBMD was measured by dual energy x-ray absorptiometry (DXA). Actigraphs worn on the non-dominant wrist were used to collect circadian activity data over 4.8 ± 0.8 consecutive 24-hour periods. An extension of the traditional cosine curve was used to fit RAR to the activity data [Ancoli-Israel et al., 2003; Marler et al., 2006]. Six RAR parameters were evaluated: acrophase (time of peak activity), amplitude (rhythm strength), mesor (mean of activity fitted curve), pseudo F-statistic (overall circadian rhythmicity of rest and activity), alpha statistic (daytime to nighttime activity ratio), and beta statistic (daytime activity). Associations between RAR and aBMD (Sleep Visit 1), and RAR and ?aBMD (Sleep Visit 1-Visit 3) were assessed with generalized linear models. Covariates included age, clinic site, physical activity, race, comorbidity, body mass index (BMI), smoking, alcohol, caffeine, beta blocker use, serum 25(OH) vitamin D and urinary melatonin and calcium. Results:Pseudo F-statistic was significantly associated with total hip aBMD (p-trend = 0.009), femoral neck aBMD (p-trend = 0.007) and total hip ?aBMD (p-trend = 0.017) in minimally adjusted models but not after multivariate (MV) adjustment. Alpha statistic was significantly associated with femoral neck aBMD (p-trend = 0.029) and femoral neck ?aBMD (p-trend = 0.019) in minimally adjusted models; significance was retained in the femoral neck ?aBMD model (p-trend = 0.034) after MV adjustment. There were no consistent, significant associations between the other RAR variables and aBMD or ?aBMD. Conclusions:The data demonstrate modest associations between overall circadian rhythmicity of rest and activity (measured by pseudo F-statistic), as well as daytime to nighttime activity ratio (measured by alpha statistic), aBMD and ?aBMD, but adjustment for covariates related to lifestyle, BMI and comorbidities attenuated most of these associations. These results suggest that RAR patterns are not independently associated with aBMD or four-year ?aBMD at the total hip or femoral neck in older men, but additional research is needed.
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