Purpose Serum level of under-carboxylated osteocalcin (ucOC) is considered a sensitive measure of... more Purpose Serum level of under-carboxylated osteocalcin (ucOC) is considered a sensitive measure of vitamin K status, and ucOC levels are associated with bone mineral density (BMD) and fracture risk in elderly persons. The aim of this study was to assess the relationship between ucOC and BMD in early menopausal women. Methods The data reported here come from the enrolment in a double-blinded placebo-controlled randomized trial comprising 334 healthy Norwegian women between 50 and 60 years, 1-5 years after menopause, not using warfarin or medication known to affect bone metabolism. Total hip, femoral neck, lumbar spine, and total body BMD and serum level of ucOC and total osteocalcin were measured, and information of lifestyle was collected through questionnaires. The association between ucOC and BMD at all measurement sites was assessed by multiple regression analyses adjusting for possible confounding variables. Results The absolute serum level of ucOC was significantly and negatively associated with BMD at all measurements sites, both in univariate analyses (p \ 0.01) and in multivariate analyses adjusting for years since menopause, smoking status and weight (p \ 0.01). However, serum ucOC, expressed as percentage of the total osteocalcin level, was not associated with BMD at any site. Conclusions Achievement of adequate vitamin K nutritional intake is important, but ucOC expressed as percentage of total osteocalcin levels as reflection of vitamin K status does not seem to play a central role in determining BMD levels in early menopausal women.
ObjectivesTo evaluate the risk of subsequent fractures in patients who attended the Fracture Liai... more ObjectivesTo evaluate the risk of subsequent fractures in patients who attended the Fracture Liaison Service (FLS), with and without incident falls after the index fracture.DesignA 3-year prospective observational cohort study.SettingAn outpatient FLS in the Netherlands.ParticipantsPatients aged 50+ years with a recent clinical fracture.Outcome measuresIncident falls and subsequent fractures.ResultsThe study included 488 patients (71.9% women, mean age: 64.6±8.6 years). During the 3-year follow-up, 959 falls had been ascertained in 296 patients (60.7%) (ie, fallers), and 60 subsequent fractures were ascertained in 53 patients (10.9%). Of the fractures, 47 (78.3%) were fall related, of which 25 (53.2%) were sustained at the first fall incident at a median of 34 weeks. An incident fall was associated with an approximately 9-fold (HR: 8.6, 95% CI 3.1 to 23.8) increase in the risk of subsequent fractures.ConclusionThese data suggest that subsequent fractures among patients on treatment ...
Clinical Reviews in Bone and Mineral Metabolism, 2014
Despite significant improvement in weight and comorbid conditions, there is growing evidence that... more Despite significant improvement in weight and comorbid conditions, there is growing evidence that bariatric surgery may exert a negative effect on the skeleton. This review has focused on the impact of bariatric surgery on bone health, with the concern that bariatric surgery may increase skeletal fragility and fracture risk by accelerating bone loss. We have highlighted studies evaluating changes in bone metabolism after three commonly performed bariatric procedures including laparoscopic adjustable gastric banding, Roux-en-Y gastric bypass surgery and increasingly popular sleeve gastrectomy. This review has also discussed some of the technical issues faced in measuring bone in obese populations and during dynamic weight loss. There is limited evidence regarding potential mechanisms for the reported observations of increased bone turnover and/or bone loss after bariatric surgery. We have reviewed the evidence surrounding potential factors affecting bone health in bariatric patients such as rapid weight loss per se, nutritional deficiencies, effects of fat-derived adipokines and gut-derived appetite-regulatory hormones. Future prospective long-term cohort studies are needed to define how to quantify bone loss in individuals with obesity, particularly following massive weight loss, and for how long the bone changes continue. These studies will help clarify any negative clinical consequences of these changes, including future fracture risk in this unique group of patients.
The Journal of Clinical Endocrinology & Metabolism, 2019
Context Although bone mineral density (BMD) is strongly associated with fracture and postfracture... more Context Although bone mineral density (BMD) is strongly associated with fracture and postfracture mortality, the burden of fractures attributable to low BMD has not been investigated. Objectives We sought to estimate the population attributable fraction of fractures and fracture-related mortality that can be attributed to low BMD. Design and Setting This study is a part of an ongoing population-based prospective cohort study, the Dubbo Osteoporosis Epidemiology study. In total, 3700 participants aged ≥50 years participated in the study. Low-trauma fracture was ascertained by X-ray reports, and mortality was ascertained from the Birth, Death and Marriage Registry. Results Overall, 21% of women and 11% of men had osteoporotic BMD. In univariable analysis, 21% and 16% of total fractures in women and men, respectively, were attributable to osteoporosis. Osteoporosis combined with advancing age (>70 years) accounted for 34% and 35% of fractures in women and men, respectively. However,...
Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the l... more Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P…
Bariatric surgery remains the most effective treatment for severely obese patients. However, the ... more Bariatric surgery remains the most effective treatment for severely obese patients. However, the potential long-term effects of bariatric surgical procedures on health, including bone health, are only partially understood. The goal of this review was to present data on the impact of bariatric surgery on bone metabolism and to analyse possible reasons for the loss of bone mass that frequently occurs after bariatric surgery. Such factors include nutritional deficiencies, rapid weight loss per se, effects of fat-derived adipokines and gut-derived appetite-regulatory hormones. However, the relative roles of these factors in skeletal regulation and the mechanisms by which they work are not yet fully defined. Our review was focussed on the complex relationship between body weight, fat mass and bone mass, as well as peripheral and central mediators potentially involved in the dual regulation of both energy and bone homeostasis. We also review the data on the inverse relationship between central obesity, bone marrow fat and osteoporosis. As the number of bariatric operations increases, it is imperative to recognize mechanisms responsible for bariatric surgery-induced bone loss, with careful monitoring of bone health including long-term fracture incidence in patients undergoing these procedures. Obesity and bone-not as simple as previously thought The prevalence of obesity worldwide has increased significantly in recent decades because of a complex range of environmental and genetic factors. Severe obesity is associated with a number of comorbid conditions and shortened life expectancy [1]. One area of research that is beginning to attract greater attention is the effect of obesity on bone. The general view among healthcare providers is that osteoporosis is not of concern for obese patients because of the known bone-strengthening effects of long-term weight bearing [2]. Indeed, epidemiological evidence suggests that obesity is correlated with increased bone mass, and that increased body weight protects against bone loss [2, 3]. However, despite such evidence of a protective effect of obesity on bone, more recent data point to a potential detrimental effect. Contrary to popular belief, osteoporosis and obesity have been shown to coexist, as evident in disorders involving fat redistribution such as type 2 diabetes mellitus, Cushing's disease and drug-induced lipodystrophies [4]. Indeed, in some cohorts, the percent of total fat mass is strongly and inversely associated with bone mineral density (BMD) [5]. Obese women have lower rates of bone formation, as indicated by circulating type I collagen levels, suggesting that increased body fat suppresses new collagen formation [6]. Besides effects on osteoporosis, BMD or bone formation rates, obesity is also associated with fractures, not only in older people. Human data show increased prevalence of forearm fractures among obese young adults as well as reduced bone mass in obese children [7, 8]. Postmenopausal obesity appears to be a risk factor for fracture at selected sites such as the tibia and ankle [9]. Moreover, there is increasing evidence to suggest that visceral obesity and the metabolic syndrome have potential detrimental effects on bone health, with a higher incidence of osteoporotic fractures and impaired bone structure and strength observed among younger and older adults with increased visceral adiposity [10, 11]. While not the focus of this review, potential mechanisms for any harmful effects of obesity on bone include the metabolic syndrome and its causes or consequences, as well as via effects on bone marrow fat. Increased fat in the bone marrow compartment is linked with
Purpose Serum level of under-carboxylated osteocalcin (ucOC) is considered a sensitive measure of... more Purpose Serum level of under-carboxylated osteocalcin (ucOC) is considered a sensitive measure of vitamin K status, and ucOC levels are associated with bone mineral density (BMD) and fracture risk in elderly persons. The aim of this study was to assess the relationship between ucOC and BMD in early menopausal women. Methods The data reported here come from the enrolment in a double-blinded placebo-controlled randomized trial comprising 334 healthy Norwegian women between 50 and 60 years, 1-5 years after menopause, not using warfarin or medication known to affect bone metabolism. Total hip, femoral neck, lumbar spine, and total body BMD and serum level of ucOC and total osteocalcin were measured, and information of lifestyle was collected through questionnaires. The association between ucOC and BMD at all measurement sites was assessed by multiple regression analyses adjusting for possible confounding variables. Results The absolute serum level of ucOC was significantly and negatively associated with BMD at all measurements sites, both in univariate analyses (p \ 0.01) and in multivariate analyses adjusting for years since menopause, smoking status and weight (p \ 0.01). However, serum ucOC, expressed as percentage of the total osteocalcin level, was not associated with BMD at any site. Conclusions Achievement of adequate vitamin K nutritional intake is important, but ucOC expressed as percentage of total osteocalcin levels as reflection of vitamin K status does not seem to play a central role in determining BMD levels in early menopausal women.
ObjectivesTo evaluate the risk of subsequent fractures in patients who attended the Fracture Liai... more ObjectivesTo evaluate the risk of subsequent fractures in patients who attended the Fracture Liaison Service (FLS), with and without incident falls after the index fracture.DesignA 3-year prospective observational cohort study.SettingAn outpatient FLS in the Netherlands.ParticipantsPatients aged 50+ years with a recent clinical fracture.Outcome measuresIncident falls and subsequent fractures.ResultsThe study included 488 patients (71.9% women, mean age: 64.6±8.6 years). During the 3-year follow-up, 959 falls had been ascertained in 296 patients (60.7%) (ie, fallers), and 60 subsequent fractures were ascertained in 53 patients (10.9%). Of the fractures, 47 (78.3%) were fall related, of which 25 (53.2%) were sustained at the first fall incident at a median of 34 weeks. An incident fall was associated with an approximately 9-fold (HR: 8.6, 95% CI 3.1 to 23.8) increase in the risk of subsequent fractures.ConclusionThese data suggest that subsequent fractures among patients on treatment ...
Clinical Reviews in Bone and Mineral Metabolism, 2014
Despite significant improvement in weight and comorbid conditions, there is growing evidence that... more Despite significant improvement in weight and comorbid conditions, there is growing evidence that bariatric surgery may exert a negative effect on the skeleton. This review has focused on the impact of bariatric surgery on bone health, with the concern that bariatric surgery may increase skeletal fragility and fracture risk by accelerating bone loss. We have highlighted studies evaluating changes in bone metabolism after three commonly performed bariatric procedures including laparoscopic adjustable gastric banding, Roux-en-Y gastric bypass surgery and increasingly popular sleeve gastrectomy. This review has also discussed some of the technical issues faced in measuring bone in obese populations and during dynamic weight loss. There is limited evidence regarding potential mechanisms for the reported observations of increased bone turnover and/or bone loss after bariatric surgery. We have reviewed the evidence surrounding potential factors affecting bone health in bariatric patients such as rapid weight loss per se, nutritional deficiencies, effects of fat-derived adipokines and gut-derived appetite-regulatory hormones. Future prospective long-term cohort studies are needed to define how to quantify bone loss in individuals with obesity, particularly following massive weight loss, and for how long the bone changes continue. These studies will help clarify any negative clinical consequences of these changes, including future fracture risk in this unique group of patients.
The Journal of Clinical Endocrinology & Metabolism, 2019
Context Although bone mineral density (BMD) is strongly associated with fracture and postfracture... more Context Although bone mineral density (BMD) is strongly associated with fracture and postfracture mortality, the burden of fractures attributable to low BMD has not been investigated. Objectives We sought to estimate the population attributable fraction of fractures and fracture-related mortality that can be attributed to low BMD. Design and Setting This study is a part of an ongoing population-based prospective cohort study, the Dubbo Osteoporosis Epidemiology study. In total, 3700 participants aged ≥50 years participated in the study. Low-trauma fracture was ascertained by X-ray reports, and mortality was ascertained from the Birth, Death and Marriage Registry. Results Overall, 21% of women and 11% of men had osteoporotic BMD. In univariable analysis, 21% and 16% of total fractures in women and men, respectively, were attributable to osteoporosis. Osteoporosis combined with advancing age (>70 years) accounted for 34% and 35% of fractures in women and men, respectively. However,...
Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the l... more Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P…
Bariatric surgery remains the most effective treatment for severely obese patients. However, the ... more Bariatric surgery remains the most effective treatment for severely obese patients. However, the potential long-term effects of bariatric surgical procedures on health, including bone health, are only partially understood. The goal of this review was to present data on the impact of bariatric surgery on bone metabolism and to analyse possible reasons for the loss of bone mass that frequently occurs after bariatric surgery. Such factors include nutritional deficiencies, rapid weight loss per se, effects of fat-derived adipokines and gut-derived appetite-regulatory hormones. However, the relative roles of these factors in skeletal regulation and the mechanisms by which they work are not yet fully defined. Our review was focussed on the complex relationship between body weight, fat mass and bone mass, as well as peripheral and central mediators potentially involved in the dual regulation of both energy and bone homeostasis. We also review the data on the inverse relationship between central obesity, bone marrow fat and osteoporosis. As the number of bariatric operations increases, it is imperative to recognize mechanisms responsible for bariatric surgery-induced bone loss, with careful monitoring of bone health including long-term fracture incidence in patients undergoing these procedures. Obesity and bone-not as simple as previously thought The prevalence of obesity worldwide has increased significantly in recent decades because of a complex range of environmental and genetic factors. Severe obesity is associated with a number of comorbid conditions and shortened life expectancy [1]. One area of research that is beginning to attract greater attention is the effect of obesity on bone. The general view among healthcare providers is that osteoporosis is not of concern for obese patients because of the known bone-strengthening effects of long-term weight bearing [2]. Indeed, epidemiological evidence suggests that obesity is correlated with increased bone mass, and that increased body weight protects against bone loss [2, 3]. However, despite such evidence of a protective effect of obesity on bone, more recent data point to a potential detrimental effect. Contrary to popular belief, osteoporosis and obesity have been shown to coexist, as evident in disorders involving fat redistribution such as type 2 diabetes mellitus, Cushing's disease and drug-induced lipodystrophies [4]. Indeed, in some cohorts, the percent of total fat mass is strongly and inversely associated with bone mineral density (BMD) [5]. Obese women have lower rates of bone formation, as indicated by circulating type I collagen levels, suggesting that increased body fat suppresses new collagen formation [6]. Besides effects on osteoporosis, BMD or bone formation rates, obesity is also associated with fractures, not only in older people. Human data show increased prevalence of forearm fractures among obese young adults as well as reduced bone mass in obese children [7, 8]. Postmenopausal obesity appears to be a risk factor for fracture at selected sites such as the tibia and ankle [9]. Moreover, there is increasing evidence to suggest that visceral obesity and the metabolic syndrome have potential detrimental effects on bone health, with a higher incidence of osteoporotic fractures and impaired bone structure and strength observed among younger and older adults with increased visceral adiposity [10, 11]. While not the focus of this review, potential mechanisms for any harmful effects of obesity on bone include the metabolic syndrome and its causes or consequences, as well as via effects on bone marrow fat. Increased fat in the bone marrow compartment is linked with
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Papers by John Eisman