To test the hypotheses that older community dwelling men taking non-enzyme-inducing antiepileptic drugs (NEIAEDs) and those taking enzyme-inducing antiepileptic drugs (EIAEDs) have increased rates of ...hip bone loss.
We ascertained antiepileptic drug (AED) use (interviewer-administered questionnaire with verification of use by containers) and measured hip bone mineral density (BMD) (using dual energy x-ray absorptiometry) at baseline and an average of 4.6 years later in a cohort of 4,222 older community-dwelling men enrolled in the Osteoporotic Fractures in Men study. Men were categorized as nonusers (no AED use at either examination, n = 4060), NEIAED user (use of NEIAED only at either examination, n = 100), or EIAED user (use of EIAED only at either examination, n = 62).
After adjustment for multiple potential confounders (age, race, clinic site, health status, pain interfering with work or activity, physical activity, smoking status, alcohol use, total calcium intake, diabetes, chronic kidney disease, vitamin D supplement use, bisphosphonate use, selective serotonin reuptake inhibitor use, inability to rise from a chair, body mass index, and baseline BMD), the average rate of decline in total hip BMD was -0.35%/year among nonusers compared with -0.53%/year among NEIAED users (p = 0.04) and -0.46%/year among EIAED users (p = 0.31). Multivariable adjusted rate of loss was -0.60%/year among men taking NEIAED at both examinations, -0.51%/year among men taking NEIAED at one examination only, and -0.35%/year among nonusers (p for trend = 0.03). Findings were similar at hip subregions.
Use of non-enzyme-inducing antiepileptic drugs was independently associated with increased rates of hip bone loss in this cohort of older community-dwelling men.
To test the hypothesis that older women with antiepileptic drug (AED) use have increased rates of bone loss.
AED use was ascertained and calcaneal and hip bone mineral density (BMD) measured in a ...cohort of 9,704 elderly community-dwelling women enrolled in the Study of Osteoporotic Fractures, and they were followed prospectively for changes in BMD. Current use of AED was assessed by interview, with verification of use from medication containers at baseline and follow-up examinations. Women were classified as continuous users, partial (intermittent) users, or nonusers. Rates of change in BMD were measured at the total hip and two subregions (average 4.4 years between examinations) and at the calcaneus (average 5.7 years between examinations).
After adjustment for confounders, the average rate of decline in total hip BMD steadily increased from -0.70%/year in nonusers to -0.87%/year in partial AED users to -1.16%/year in continuous AED users (p value for trend = 0.015). Higher rates of bone loss were also observed among continuous AED users at subregions of the hip and at the calcaneus. In particular, continuous phenytoin users had an adjusted 1.8-fold greater mean rate of loss at the calcaneus compared with nonusers of AED (-2.68 vs -1.46%/year; p < 0.001) and an adjusted 1.7-fold greater mean rate of loss at the total hip compared with nonusers of AED (-1.16 vs -0.70%/year; p = 0.069).
Continuous AED use in elderly women is associated with increased rates of bone loss at the calcaneus and hip. If unabated, the rate of hip bone loss among continuous AED users is sufficient to increase the risk of hip fracture by 29% over 5 years among women age 65 years and older.
Summary
There is limited wrist fracture information on men. Our goal was to calculate frequency and identify risk factors for wrist fracture in the Osteoporotic Fractures in Men (MrOS) study. We ...confirmed that fracture history and certain medications are predictors, and identified novel predictors including markers of kidney function and physical performance.
Introduction
To calculate the incidence of wrist fractures and their risk factors in older community-dwelling men from the US Osteoporotic Fractures in Men (MrOS) study.
Methods
Using triannual postcards, we identified incident wrist fractures (centrally confirmed by radiology) in men aged ≥ 65. Potential risk factors included the following: demographics, lifestyle, bone mineral density (BMD), selected medications, biomarkers, and physical function and performance measures. Both baseline and time-varying models were adjusted for age, race/ethnicity, MrOS geographic location, and competing mortality risks.
Results
We observed 97 incident wrist fractures among 5875 men followed for an average of 10.8 years. The incidence of wrist fracture was 1.6 per 1000 person-years overall and ranged from 1.0 among men aged 65–69 to 2.4 among men age ≥ 80. Significant predictors included the following: fracture history after age 50 hazard ratio (95% CI): 2.48 (1.65, 3.73), high serum phosphate 1.25 (1.02, 1.53), use of selective serotonin receptor inhibitor (SSRI) 3.60 (1.96, 6.63), decreased right arm BMD 0.49 (0.37, 0.65) per SD increase, and inability to perform the grip strength test 3.38 (1.24, 9.25). We did not find associations with factors commonly associated with wrist and other osteoporosis fractures like falls, diabetes, calcium and vitamin D intake, and alcohol intake.
Conclusions
Among these older, community-dwelling men, we confirmed that fracture history is a strong predictor of wrist fractures in men. Medications such as SSRIs and corticosteroids also play a role in wrist fracture risk. We identified novel risk factors including kidney function and the inability to perform the grip strength test.
Summary
We investigated 383 bone candidate genes for associations between single nucleotide polymorphisms and vertebral trabecular volumetric bone mineral density (vBMD) and cross-sectional area ...(CSA) in 2,018 Caucasian men aged ≥65 years. SNPs in
TGFBR3
,
SOST
,
KL
,
CALCR
,
LEP
,
CSF1R
,
PTN
,
GNRH2
,
FGFR2
, and
MEPE
were associated with vBMD and SNPs in
CYP11B1
,
DVL2
,
DLX5
,
WNT4
, and
PAX7
were associated with CSA in independent study samples (
p
< 0.005).
Inroduction
Vertebral bone mineral density and cross-sectional area are important determinants of vertebral bone strength. Little is known about the specific genetic variants that influence these phenotypes in humans.
Methods
We investigated the potential genetic variants associated with vertebral trabecular volumetric BMD and CSA measured by quantitative computed tomography. We initially tested for association between these phenotypes and 4608 tagging and potentially functional single nucleotide polymorphisms (SNPs) in 383 candidate genes in 862 community-dwelling Caucasian men aged ≥65 years in the Osteoporotic Fractures in Men Study.
Results
SNP associations were then validated by genotyping an additional 1,156 randomly sampled men from the same cohort. We identified 11 SNPs in 10 genes (
TGFBR3
,
SOST
,
KL
,
CALCR
,
LEP
,
CSF1R
,
PTN
,
GNRH2
,
FGFR2
, and
MEPE
) that were consistently associated with trabecular vBMD and five SNPs in five genes (
CYP11B1
,
DVL2
,
DLX5
,
WNT4
, and
PAX7
) that were consistently associated with CSA in both samples (
p
< 0.005).
Conclusion
None of the SNPs associated with trabecular vBMD were associated with CSA. Our findings raise the possibility that at least some of the loci for vertebral trabecular BMD and bone size may be distinct.
It is unknown whether treatment for osteoporosis with raloxifene is safe or effective in those with chronic kidney disease (CKD). With data from a multicenter, randomized, placebo-controlled trial of ...7705 postmenopausal women with osteoporosis, the effect of raloxifene on rate of change of bone mineral density (BMD), incidence of fractures, and adverse events by stage of CKD was examined over 3 yr. Baseline serum creatinine values were available for 7316 women, and these values were used to assign a category of creatinine clearance (CrCl) using the Cockcroft-Gault formula (CrCl < 45, 45 to 59, and > or = 60 ml/min). BMD was measured at baseline and annually by dual x-ray absorptiometry. Within the placebo group, lower baseline CrCl was associated with a trend for higher annual losses of BMD at the femoral neck; however, within the raloxifene group, lower baseline CrCl was associated with greater increases in femoral neck BMD. This interaction between category of CrCl and treatment assignment was significant for rate of change of BMD at the hip. Irrespective of kidney function, raloxifene treatment was associated with a greater increase in spine BMD, a reduction in vertebral fractures, and no effect on nonvertebral fractures compared with placebo. Within each category of kidney function, adverse events were similar between the raloxifene and placebo groups. In conclusion, raloxifene increases BMD at both the hip and the spine and reduces the risk for vertebral fractures among individuals with CKD. The effect ofraloxifene on hip BMD is greater among those with mild to moderate CKD.
Direct assessment of skeletal muscle mass in older adults is clinically challenging. Relationships between lean mass and late-life outcomes have been inconsistent. The D3-creatine dilution method ...provides a direct assessment of muscle mass.
Muscle mass was assessed by D3-creatine (D3Cr) dilution in 1,382 men (mean age, 84.2 years). Participants completed the Short Physical Performance Battery (SPPB); usual walking speed (6 m); and dual x-ray absorptiometry (DXA) lean mass. Men self-reported mobility limitations (difficulty walking 2-3 blocks or climbing 10 steps); recurrent falls (2+); and serious injurious falls in the subsequent year. Across quartiles of D3Cr muscle mass/body mass, multivariate linear models calculated means for SPPB and gait speed; multivariate logistic models calculated odds ratios for incident mobility limitations or falls.
Compared to men in the highest quartile, those in the lowest quartile of D3Cr muscle mass/body mass had slower gait speed (Q1: 1.04 vs Q4: 1.17 m/s); lower SPPB (Q1: 8.4 vs Q4: 10.4 points); greater likelihood of incident serious injurious falls (odds ratio OR Q1 vs Q4: 2.49, 95% confidence interval CI: 1.37, 4.54); prevalent mobility limitation (OR Q1 vs Q4,: 6.1, 95% CI: 3.7, 10.3) and incident mobility limitation (OR Q1 vs Q4: 2.15 95% CI: 1.42, 3.26); p for trend < .001 for all. Results for incident recurrent falls were in the similar direction (p = .156). DXA lean mass had weaker associations with the outcomes.
Unlike DXA lean mass, low D3Cr muscle mass/body mass is strongly related to physical performance, mobility, and incident injurious falls in older men.
Abstract
Context
Studies of the possible cardiovascular risk of testosterone treatment are inconclusive.
Objective
To determine the effect of testosterone treatment on cardiovascular biomarkers in ...older men with low testosterone.
Design
Double-blind, placebo-controlled trial.
Setting
Twelve academic medical centers in the United States.
Participants
In all, 788 men ≥65 years old with an average of two serum testosterone levels <275 ng/dL who were enrolled in The Testosterone Trials.
Intervention
Testosterone gel, the dose adjusted to maintain the testosterone level in the normal range for young men, or placebo gel for 12 months.
Main Outcome Measures
Serum markers of cardiovascular risk, including lipids and markers of glucose metabolism, fibrinolysis, inflammation, and myocardial damage.
Results
Compared with placebo, testosterone treatment significantly decreased total cholesterol (adjusted mean difference, −6.1 mg/dL; P < 0.001), high-density lipoprotein cholesterol (adjusted mean difference, −2.0 mg/dL; P < 0.001), and low-density lipoprotein cholesterol (adjusted mean difference, −2.3 mg/dL; P = 0.051) from baseline to month 12. Testosterone also slightly but significantly decreased fasting insulin (adjusted mean difference, −1.7 µIU/mL; P = 0.02) and homeostatic model assessment‒insulin resistance (adjusted mean difference, −0.6; P = 0.03). Testosterone did not change triglycerides, d-dimer, C-reactive protein, interleukin 6, troponin, glucose, or hemoglobin A1c levels more than placebo.
Conclusions and Relevance
Testosterone treatment of 1 year in older men with low testosterone was associated with small reductions in cholesterol and insulin but not with other glucose markers, markers of inflammation or fibrinolysis, or troponin. The clinical importance of these findings is unclear and requires a larger trial of clinical outcomes.
Compared with placebo, testosterone treatment of older men with low testosterone was associated with small reductions in total, HDL, and LDL cholesterol and in insulin and HOMA-IR but not glucose.
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