Project description:BackgroundBack pain poses a significant global burden, within which individuals with more severe symptoms consume higher healthcare expenses than those with lesser back pain. Whether measures of body composition predict high-intensity back pain and/or high-disability in population-based cohorts is unknown. This study aimed to examine the association between body composition at baseline and their change in the prior 5 years (between 2001-2005 and 2006-2010) and incident high-intensity back pain and/or high-disability in long-term follow-up, 10 years later (2016-2021) in a population-based cohort of men.MethodThis study examined men with no or low-intensity back pain and disability (Graded Chronic Pain Scale) at back pain study baseline (2006-2010) within the Geelong Osteoporosis Study. Those developing high-intensity pain and/or high disability at follow-up (2016-2021) were identified. Weight, body mass index (BMI), abdominal circumferences, fat mass and lean mass (dual energy X-ray absorptiometry) were assessed prebaseline (2001-2005) and at baseline. The association of body composition at baseline and change in body composition from prebaseline to baseline with incident high-intensity pain and/or high disability at follow-up were examined using multivariable logistic regression.ResultOf 695 participants with no or low-intensity pain and disability at baseline, 441 (62.3%) completed follow-up with a mean age of 54.3 ± 14.1 years: 37 (8.3%) developed high-intensity pain and/or high-disability, 33 (7.5%) developed high-intensity pain and 14 (3.2%) high disability. No measures of body composition at baseline were associated with incident high-intensity pain and/or high disability at follow-up in the whole population. In subgroup analysis, among men aged over 60 years, but not younger, higher lean mass was associated with decreased likelihood of high-intensity pain and/or high-disability (odds ratio [OR] 0.86, 95% confidence interval [CI] 0.76, 0.97, interaction p < 0.001). In the whole population, examination of the relationship between change in measures of body composition between prebaseline and baseline, only a one unit increase in BMI, equivalent to 3.1-kg weight gain, was associated with increased incident high disability (OR 1.63, 95% CI 1.06, 2.51).ConclusionIn a population-based sample, without severe back pain and disability, in older men aged ≥60 years, higher lean mass was protective of incident high-intensity pain and/or high disability. An increase in BMI, over 5 years, equivalent to 3.1-kg weight gain, was associated with incident back pain related high disability 10 years later. These results demonstrate another detrimental consequence of weight gain and highlight the importance of maintaining muscle mass in older men.
Project description:ObjectiveAlthough negative back beliefs are associated with high-intensity low back pain (LBP)/disability, whether they influence incident high-intensity LBP/high-disability over the long-term is unknown. This study aimed to investigate whether negative back beliefs were associated with developing high-intensity LBP and/or high-disability over 10 years in men.MethodsMen with no or low-intensity LBP and/or disability attending the Geelong Osteoporosis Study between 2006-2010 were included. Data on age, body mass index, mobility, education, back beliefs (Back Beliefs Questionnaire), LBP and disability (Graded Chronic Pain Scale) were collected between 2006-2010. Beliefs, LBP and disability were re-assessed in 2016-2021. Binary logistic regression was used to examine the association between negative back beliefs and incident high-intensity pain and/or high-disability, adjusting for age, body mass index, mobility, and education.ResultsAt baseline, 705 participants (mean age 53.8 years) had no or low LBP and no or low-disability; 441 (62.6%) participants completed a 10-year follow-up. Of these, 37 (8.4%) developed high-intensity pain and/or high-disability. In multivariate analyses, participants with more negative back beliefs at baseline were more likely to develop high-intensity pain and/or high-disability (Odds ratio 1.05, 95% CI 1.00-1.11). Developing more negative back beliefs was also associated with incident high-intensity pain and/or high-disability (Odds Ratio 1.20, 95% CI 1.12-1.30).ConclusionIn a male community-based population, negative beliefs regarding the consequences of LBP were associated with an increased likelihood of developing high-intensity pain and/or high-disability. Addressing negative back beliefs in the community may reduce the incidence of high-intensity pain and/or high-disability over 10 years in men.
Project description:BackgroundSevere gonadal steroid deficiency induces bone loss in adult men; however, the specific roles of androgen and estrogen deficiency in hypogonadal bone loss are unclear. Additionally, the threshold levels of testosterone and estradiol that initiate bone loss are uncertain.MethodsOne hundred ninety-eight healthy men, ages 20-50, received goserelin acetate, which suppresses endogenous gonadal steroid production, and were randomized to treatment with 0, 1.25, 2.5, 5, or 10 grams of testosterone gel daily for 16 weeks. An additional cohort of 202 men was randomized to receive these treatments plus anastrozole, which suppresses conversion of androgens to estrogens. Thirty-seven men served as controls and received placebos for goserelin and testosterone. Changes in bone turnover markers, bone mineral density (BMD) by dual-energy x-ray absorptiometry (DXA), and BMD by quantitative computed tomography (QCT) were assessed in all men. Bone microarchitecture was assessed in 100 men.ResultsAs testosterone dosage decreased, the percent change in C-telopeptide increased. These increases were considerably greater when aromatization of testosterone to estradiol was also suppressed, suggesting effects of both testosterone and estradiol deficiency. Decreases in DXA BMD were observed when aromatization was suppressed but were modest in most groups. QCT spine BMD fell substantially in all testosterone-dose groups in which aromatization was also suppressed, and this decline was independent of testosterone dose. Estradiol deficiency disrupted cortical microarchitecture at peripheral sites. Estradiol levels above 10 pg/ml and testosterone levels above 200 ng/dl were generally sufficient to prevent increases in bone resorption and decreases in BMD in men.ConclusionsEstrogens primarily regulate bone homeostasis in adult men, and testosterone and estradiol levels must decline substantially to impact the skeleton.Trial registrationClinicalTrials.gov, NCT00114114.FundingAbbVie Inc., AstraZeneca Pharmaceuticals LP, NIH.
Project description:Osteoporosis is a medical condition of global concern, with increasing incidence in both sexes. Bone mineral density (BMD), a highly heritable trait, has been proven a useful diagnostic factor in predicting fracture. Because medical information is lacking about male osteoporotic genetics, we conducted a genome-wide association study of BMD in Korean men. With 1,176 participants, we analyzed 4,414,664 single nucleotide polymorphisms (SNPs) after genomic imputation, and identified five SNPs and three loci correlated with bone density and strength. Multivariate linear regression models were applied to adjust for age and body mass index interference. Rs17124500 (p = 6.42 × 10(-7)), rs34594869 (p = 6.53 × 10(-7)) and rs17124504 (p = 6.53 × 10(-7)) in 14q31.3 and rs140155614 (p = 8.64 × 10(-7)) in 15q25.1 were significantly associated with lumbar spine BMD (LS-BMD), while rs111822233 (p = 6.35 × 10(-7)) was linked with the femur total BMD (FT-BMD). Additionally, we analyzed the relationship between BMD and five genes previously identified in Korean men. Rs61382873 (p = 0.0009) in LRP5, rs9567003 (p = 0.0033) in TNFSF11 and rs9935828 (p = 0.0248) in FOXL1 were observed for LS-BMD. Furthermore, rs33997547 (p = 0.0057) in ZBTB and rs1664496 (p = 0.0012) in MEF2C were found to influence FT-BMD and rs61769193 (p = 0.0114) in ZBTB to influence femur neck BMD. We identified five SNPs and three genomic regions, associated with BMD. The significance of our results lies in the discovery of new loci, while also affirming a previously significant locus, as potential osteoporotic factors in the Korean male population.
Project description:BackgroundDisrupted 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.MethodsMrOS 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 ΔaBMD (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.ResultsPseudo F-statistic was significantly associated with total hip aBMD (p-trend = 0.009), femoral neck aBMD (p-trend = 0.007) and total hip ΔaBMD (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 ΔaBMD (p-trend = 0.019) in minimally adjusted models; significance was retained in the femoral neck ΔaBMD model (p-trend = 0.034) after MV adjustment. There were no consistent, significant associations between the other RAR variables and aBMD or ΔaBMD.ConclusionsThe 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 ΔaBMD, 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 ΔaBMD at the total hip or femoral neck in older men, but additional research is needed.
Project description:Mounting evidence correlate vitamin D3 (cholecalciferol) supplementation or higher serum levels of vitamin D (25(OH)D) with a lower risk of developing multiple sclerosis (MS), reduced relapse rate, slower progression or fewer new brain lesions. We present here the case of a woman who was diagnosed with MS in 1990. From 1980 to 2000, her ability to walk decreased from ~20 to 1 km per day. Since January 2001, a vitamin D3 supplement was ingested daily. The starting dose was 20 mcg (800 IU)/day and escalated to 100 mcg (4000 IU)/day in September 2004 and then to 150 mcg (6000 IU)/day in December 2005. Vitamin D3 intake reduced muscular pain and improved ambulation from 1 (February 2000) to 14 km/day (February 2008). Vitamin D intake over 10 years caused no adverse effects: no hypercalcaemia, nephrolithiasis or hypercalciuria were observed. Bowel problems in MS may need to be addressed as they can cause malabsorption including calcium, which may increase serum PTH and 1,25(OH)2D levels, as well as bone loss. We suggest that periodic assessment of vitamin D3, calcium and magnesium intake, bowel problems and the measurement of serum 25(OH)D, PTH, Ca levels, UCa/Cr and bone health become part of the integral management of persons with MS.
Project description:BackgroundVitamin K modulates cytokines involved in bone turnover, including interleukin-6 (IL-6) and osteoprotegerin in vitro.ObjectiveThe objective of this study was to assess 1) associations between measures of vitamin K status [plasma phylloquinone and serum percentage of undercarboxylated osteocalcin (%ucOC)] and IL-6, osteoprotegerin, and C-reactive protein (CRP) concentrations and 2) the effect of daily 500 mug phylloquinone supplementation for 3 y on cytokine concentrations.DesignConcentrations of IL-6, osteoprotegerin, and CRP and bone mineral density (BMD) were measured at baseline and after 3 y of follow-up in 379 healthy men and women (60-81 y; 58.5% women) participating in a randomized trial that studied the effect of vitamin K supplementation on bone loss.ResultsCross-sectionally, plasma phylloquinone was inversely associated with IL-6 and CRP, whereas serum %ucOC was inversely associated with IL-6. Osteoprotegerin was associated positively with plasma phylloquinone and inversely with %ucOC. No differences were observed in the 3-y change in IL-6, osteoprotegerin, and CRP concentrations between participants who received phylloquinone supplementation and those who did not. Overall, no association was observed between the 3-y changes in circulating cytokines and BMD.ConclusionsPoor vitamin K status was associated with high concentrations of cytokines involved in bone turnover, but vitamin K supplementation did not confer a decrease in cytokine concentrations. The healthy status of this cohort may explain a lack of effect of vitamin K supplementation on cytokine concentrations. This trial was registered with www.clinicaltrials.gov as NCT00183001.
Project description:Studying dietary patterns is often more informative than individual nutrients or foods. We found that a Prudent dietary pattern (rich in vegetables and fish) was associated with reduced loss of total hip BMD in older men. A Prudent dietary pattern may be a potential lifestyle strategy for minimizing bone loss. INTRODUCTION:This study aimed to identify baseline dietary patterns using factor analysis in a cohort of older men and to evaluate whether the dietary patterns were associated with bone mineral density change (%ΔBMD) at the total hip and femoral neck over time. METHODS:Participants (n = 4379; mean age 72.9 ± 5.5 years) were from the Osteoporotic Fractures in Men (MrOS) prospective cohort study and had dietary data collected at baseline (March 2000-April 2002) and BMD measured at baseline and Visit 2 (March 2005-May 2006). Dietary intake was assessed with a brief Block food frequency questionnaire (FFQ); factor analysis was used to derive dietary patterns. BMD was measured by dual-energy x-ray absorptiometry (DXA); %ΔBMD was calculated from baseline to Visit 2. We used generalized linear regression to estimate least square (LS) means of %ΔBMD in quartiles of the dietary pattern scores adjusted for potential confounding factors. RESULTS:Two major dietary patterns were derived: Prudent (abundant in vegetables, salad, and non-fried fish) and Western (rich in hamburger, fries, processed meats, cheese, and sweets/desserts). There was an inverse association between adherence to the Prudent pattern and total hip %ΔBMD (p-trend = 0.028 after adjusting for age and clinical site; p-trend = 0.033 after further adjustment for smoking, calcium supplement use, diabetes, hypertension, and total energy intake). No other consistent associations between dietary patterns and %ΔBMD were observed. CONCLUSIONS:Greater adherence to a Prudent dietary pattern may attenuate total hip BMD loss (%ΔBMD) in older men.