Eating disorders,menstrual dysfunction,weight change and DMPA use predict bone density change in college-aged women

IntroductionThere are limited longitudinal studies that have evaluated bone mineral density (BMD) changes in college-aged women. Our objective was to simultaneously evaluate factors influencing 4-year BMD change.MethodsThis was a longitudinal cohort study of healthy, physically active women in the US Military Academy (n = 91; average age = 18.4 years). Assessments over four years included: height, weight, calcium intake, physical fitness, menstrual function (annual number cycles), oral contraceptives (OCs) or depot-medroxyprogesterone acetate (DMPA) use, and eating disorder behavior (Eating Disorder Inventory; (EDI)). BMD was measured annually at the lumbar spine and total hip by dual X-ray absorptiometry and calcaneal BMD by PIXI. Slope of 4 year BMD change at each skeletal site (spine total hip and calcaneus) was calculated for each woman.ResultsBMD gains occurred at the spine in 50% and the hip in 36% of women. In unadjusted analyses, spine bone gain was positively related to menstrual cycle frequency (p = 0.04). Spine and hip BMD loss occurred in those using DMPA (p < 0.01) and those with the highest EDI quartile scores (p < 0.05). BMD change was unrelated to OC use. Hip and calcaneus BMD decreased with weight loss (average 4.8 + 2.2 lb/year) as compared to those with stable weight/weight gain (p < 0.05). In multivariable analysis, spine BMD increase was significantly related to African American (AA) race, normal EDI score and normal menses. Hip BMD increase was related to AA race, weight increase and normal menses. DMPA use was associated with spine, hip, and calcaneus bone loss.ConclusionOn average, BMD may modestly increase in college-aged women, in the absence of risk factors. However, risk factors including subclinical eating disorders, weight loss, menstrual dysfunction and DMPA use can have significant detrimental effects on BMD in young healthy physically active women.     

Use of selective serotonin reuptake inhibitors and bone mass in adolescents: An NHANES study

ContextSelective serotonin reuptake inhibitors (SSRIs) are commonly prescribed medications to treat depression and anxiety. SSRIs exert their effects by inhibiting the serotonin transporter and modulating extracellular serotonin levels, a neurotransmitter that has been shown to affect bone metabolism in animals. Studies in adults suggest a negative association between SSRI use and bone mineral density (BMD), greater rates of bone loss with SSRI use and increased risk of fractures. However, the results on bone mass have been inconsistent. Furthermore, there is a dearth of studies examining an association between SSRI use and bone mass in the pediatric and adolescent age group.ObjectiveTo investigate associations between SSRI use and bone mass in adolescents.DesignCross-sectional analysis of data from the 2005–2010 National Health and Nutrition Examination Study (NHANES).Participants4303 NHANES participants aged 12–20 years. The mean age was 15.65 ± 2.42 years.Main outcomesTotal femur, femoral neck and lumbar spine bone mineral content (BMC) and BMD assessed via dual-energy X-ray absorptiometry (DXA).Results62 out of 4303 subjects used SSRIs. SSRI use was an independent predictor of bone mass after adjusting for age, gender, height and weight Z score, socioeconomic status, physical activity, serum cotinine level and race/ethnicity. After multivariable adjustment, total femur BMC was 8.8% lower among SSRI users versus non-users (mean difference 2.98 g, SE ± 0.105 g, p = 0.0006), while total femur BMD was 6.1% lower (mean difference 0.06 g/cm², SE ± 0.002 g/cm², p = 0.016). Femoral neck BMC and BMD and lumbar spine BMC were similarly negatively associated with SSRI use. Compared to nonusers, lumbar spine BMC was 7% lower among SSRI users (mean difference 0.97 g, SE ± 0.048 g, p = 0.02) and BMD was 3.2% lower (mean difference 0.03 g/cm², SE ± 0.015 g/cm², p = 0.09). Sub-analysis of those individuals treated for more than 6 months yield similar results. Finally, the association of SSRIs with bone mass persisted after excluding individuals with Body Mass Index (BMI) less than 5th percentile thus accounting for the possible confounding effect of anorexia nervosa, which can be treated with SSRIs.ConclusionIn this NHANES study, adolescents treated with SSRIs had lower DXA measurements of the total femur and lumbar spine compared to SSRI non-users. These findings support the need for future prospective studies to examine the effects of SSRI use on bone mass in adolescents.     

Baseline MRI inflammation is not a determinant of 5-year bone mineral density loss in patients with early spondyloarthritis

ObjectiveThe aim of this study was to assess the effect of baseline inflammation on Magnetic Resonance Imaging (MRI) on the change in Bone Mineral Density (BMD) over 5 years in patients with early spondyloarthritis (SpA).MethodsFrom the patients of the DESIR cohort (an early axial SpA cohort), patients with BMD data at both baseline and 5 years, and baseline spine and sacroiliac joints MRI were included. Inflammation was assessed with the SpondyloArthritis Research Consortium of Canada (SPARCC) spine score. Significant BMD loss was defined by a change of > 0.03 g/cm². No patients had received TNF blockers before inclusion in the cohort. Univariate and multivariable prognostic analyses were performed. An inverse propensity score weighting method was used to handle confounders.ResultsOne hundred and eighty-three patients were included (mean age 33.9 ± 8.7 years, 58.5% men). A significant bone loss was reported in 51% (n = 92) of patients at either lumbar spine or hip. Fourteen (7%) patients had low BMD (Z-score < −2) at the end of the follow-up vs. 28 (15%) at baseline. In multivariable analysis, age was a protective factor of 5 year-BMD loss at any site (OR = 0.96, 95% CI [0.93–0.99]). Baseline MRI inflammation has no significant effect on BMD change at any site (OR= 0.84, 95% CI [0.46–1.53]).ConclusionHalf of patients with early SpA have a significant bone loss at either lumbar spine or hip over 5 years. Baseline MRI inflammation is not a determinant of this bone loss.     

Racial differences in bone loss and relation to menopause among HIV-infected and uninfected women

ObjectiveTo characterize changes in bone mineral density (BMD) according to race among HIV-infected and uninfected women, and to evaluate the relationship between race and menopause-related bone loss.MethodsDual X-ray absorptiometry measured BMD on study entry and a minimum of 18 months later in 246 HIV-infected and 219 HIV-uninfected women in the Menopause Study. Linear regression analyses determined percent annual BMD change at the total hip (TH), femoral neck (FN), and lumbar spine (LS) after adjusting for potential confounders. Race-stratified and HIV-infected subgroup analyses were performed.ResultsAt baseline, mean age was 45 years, 19% of women were postmenopausal. HIV-infected women were more likely to be black (58% vs. 38%), and had lower BMI and less cigarette exposure when compared to HIV-uninfected women. Women who were perimenopausal at baseline and postmenopausal at follow-up had the greatest TH bone loss (− 1.68%/yr, p < .0001) followed by those postmenopausal throughout (− 1.02%/yr, p = .007). We found a significant interaction between HIV status and race in multivariate analyses of BMD change at the FN and TH. In race-stratified analyses, HIV infection was associated with TH BMD loss in non-black women. Black women experienced greater menopause-associated decline in TH BMD compared with non-black women.ConclusionsThe association of HIV and BMD differs strikingly by race, as do the effects of the menopausal transition on bone. Determining the extent to which the effect of HIV on fracture risk varies by race will be crucial to identify HIV-infected women at greatest risk for osteoporotic fracture, particularly as they enter menopause.     

Low grade inflammation is associated with lower velocity of sound and broadband ultrasound attenuation in older men,but not with bone loss or fracture risk in a longitudinal aging study

ObjectivesElevated systemic levels of pro-inflammatory cytokines involved in the pathogenesis of osteoporosis. Our objective was to investigate whether low grade systemic inflammation was associated with bone markers, bone quality, bone mass and fracture risk in a population of older persons.MethodsSerum interleukin 6 (IL-6), high-sensitivity C-reactive protein (hsCRP) and erythrocyte sedimentation rate (ESR) were measured in 1287 participants of the Longitudinal Aging Study Amsterdam (LASA), a population based study in a representative sample of older men and women (age 76 ± 6.7 years). Bone quality was measured by quantitative ultrasound measurements (QUS) at baseline and after 3 years at the calcaneus, and bone mineral density was measured by dual-energy X-ray absorptiometry (DXA) at the spine and hip in a subpopulation. Furthermore, the bone markers osteocalcin (OC) and urinary excretion of deoxypyridinoline (DPD) were determined. Incident clinical fractures were recorded during 6 years of follow-up.ResultsMultivariable regression analyses revealed higher IL-6 and ESR levels were associated with lower quantitative ultrasound values in older men (β = − 0.98; 95% CI − 57.72 to − 6.42, p < 0.05) and (β = − 0.221; 95% CI − 15.39 to − 3.27, p < 0.05) respectively at baseline, but not in women. No significant associations were found between inflammatory markers and bone markers, bone loss at the spine or hips, fracture rate or time to fracture.ConclusionElevated inflammatory markers are associated with impaired bone quality in older men, but not in women. No associations were found with the risk for fractures.     

Contribution of Serum Inflammatory Markers to Changes in Bone Mineral Content and Density in Postmenopausal Women: A 1-Year Investigation

Bone formation and resorption are influenced by inflammatory processes. We examined the relationships among inflammatory markers and bone mineral content (BMC) and density (BMD) and determined the contribution of inflammatory markers to 1-yr changes in BMC and BMD in healthy postmenopausal women. This analysis included 242 women at baseline from our parent Soy Isoflavones for Reducing Bone Loss project who were randomly assigned to 1 of 3 treatment groups: placebo, 80 mg/d soy isoflavones, or 120 mg/d soy isoflavones. BMD and BMC from the lumbar spine (LS), total proximal femur (hip), and whole body were measured by dual energy X-ray absorptiometry and the 4% distal tibia by peripheral quantitative computed tomography. Serum inflammatory markers (C-reactive protein, interleukin [IL]-1β, IL-6, tumor necrosis factor-alpha [TNF-α], and white blood cell count [WBC]) were measured at baseline, 6, and 12 mo. Because of attrition or missing values, data analysis at 12 mo includes only 235 women. Significant associations among IL-6, TNF-α, and WBC were observed with percent change in LS, hip, and whole body BMC and BMD. Multiple regression analysis indicated that in combination inflammatory markers accounted for 1.1–6.1% of the variance to the observed 12-mo changes in BMC and BMD. Our results suggest that modifying inflammatory markers, even in healthy postmenopausal women, may possibly reduce bone loss.     

Regional fat depots and their relationship to bone density and microarchitecture in young oligo-amenorrheic athletes

ContextVarious fat depots have differential effects on bone. Visceral adipose tissue (VAT) is deleterious to bone, whereas subcutaneous adipose tissue (SAT) has positive effects. Also, marrow adipose tissue (MAT), a relatively newly recognized fat depot is inversely associated with bone mineral density (BMD). Bone mass in athletes depends on many factors including gonadal steroids and muscle mass. Exercise increases muscle mass and BMD, whereas, estrogen deficiency decreases BMD. Thus, the beneficial effects of weight-bearing exercise on areal and volumetric BMD (aBMD and vBMD) in regularly menstruating (eumenorrheic) athletes (EA) are attenuated in oligo-amenorrheic athletes (OA). Of note, data regarding VAT, SAT, MAT and regional muscle mass in OA compared with EA and non-athletes (C), and their impact on bone are lacking.MethodsWe used (i) MRI to assess VAT and SAT at the L4 vertebra level, and cross-sectional muscle area (CSA) of the mid-thigh, (ii) 1H-MRS to assess MAT at L4, the proximal femoral metaphysis and mid-diaphysis, (iii) DXA to assess spine and hip aBMD, and (iv) HRpQCT to assess vBMD at the distal radius (non-weight-bearing bone) and tibia (weight-bearing bone) in 41 young women (20 OA, 10 EA and 11 C 18–25 years). All athletes engaged in weight-bearing sports for ≥ 4 h/week or ran ≥ 20 miles/week.Main outcome measuresVAT, SAT and MAT at L4; CSA of the mid-thigh; MAT at the proximal femoral metaphysis and mid-diaphysis; aBMD, vBMD and bone microarchitecture.ResultsGroups had comparable age, menarchal age, BMI, VAT, VAT/SAT and spine BMD Z-scores. EA had higher femoral neck BMD Z-scores than OA and C. Fat mass was lowest in OA. SAT was lowest in OA (p = 0.048); L4 MAT was higher in OA than EA (p = 0.03). We found inverse associations of (i) VAT/SAT with spine BMD Z-scores (r = − 0.42, p = 0.01), (ii) L4 MAT with spine and hip BMD Z-scores (r = − 0.44, p = 0.01; r = − 0.36, p = 0.02), and vBMD of the radius and tibia (r = − 0.49, p = 0.002; r = − 0.41, p = 0.01), and (iii) diaphyseal and metaphyseal MAT with vBMD of the radius (r ≤ − 0.42, p ≤ 0.01) and tibia (r ≤ − 0.34, p ≤ 0.04). In a multivariate model including VAT/SAT, L4 MAT and thigh CSA, spine and hip BMD Z-scores were predicted inversely by L4 MAT and positively by thigh CSA, and total and cortical radius and total tibial vBMD were predicted inversely by L4 MAT. VAT/SAT did not predict radius or tibia total vBMD in this model, but inversely predicted spine BMD Z-scores. When L4 MAT was replaced with diaphyseal or metaphyseal MAT in the model, diaphyseal and metaphyseal MAT did not predict aBMD Z-scores, but diaphyseal MAT inversely predicted total vBMD of the radius and tibia. These results did not change after adding percent body fat to the model.ConclusionsVAT/SAT is an inverse predictor of lumbar spine aBMD Z-scores, while L4 MAT is an independent inverse predictor of aBMD Z-scores at the spine and hip and vBMD measures at the distal tibia and radius in athletes and non-athletes. Diaphyseal MAT independently predicts vBMD measures of the distal tibia and radius.     

Effects of milk salt supplementation on bone mineral gain in pubertal Chinese adolescents: A 2-year randomized,double-blind,controlled, dose–response trial

Background/objectiveAdequate calcium intakes may enhance bone mineral accumulation during childhood. Little is known about the optimal calcium intake in Chinese adolescents. We examined the effects of three levels of calcium intake on bone mineral accretion in adolescents.MethodsThis was a 2-year randomized, double-blind, controlled trial. The subjects were randomly assigned to receive 40 g of milk powder containing 300 mg of calcium and 200 IU of vitamin D (Low-Ca group), or same milk powder additionally fortified with 300 mg of calcium (Mid-Ca group) or 600 mg of calcium (High-Ca group) for 2 years. The subjects' bone mineral density (BMD) and bone mineral content (BMC) at the total body, lumbar spine and left hip were determined by dual-energy X-ray absorptiometry at baseline and after the second year of treatment. Of the 111 girls and 109 boys (aged 12–14 years) enrolled, 91 girls and 91 boys completed the trial.ResultsThe girls in the High-Ca group (1,110 mg/d) had 2.3%, 2.7% and 2.6% greater BMD accretion at the total hip, femoral neck and shaft (P < 0.05) but not at total body less head and spine than those in the Low-Ca group (655 mg/d). A significant effect of higher calcium intake was also observed for percentage change of size-adjusted BMC at femur neck (P = 0.047). Bonferroni tests indicated no significant differences in the percentage changes in BMD, BMC or size-adjusted BMC between the Mid- and Low-Ca groups and between the High- and Mid-Ca groups. Extra calcium had no observable additional effect in the boys (P > 0.05).ConclusionAn intake of 1000 mg/d or more might be helpful in maximizing bone mineral accretion in the hip for girls. But further large studies are required to identify its long-term effects and the optimal calcium intake for boys.     

Risedronate may preserve bone microarchitecture in breast cancer survivors on aromatase inhibitors: A randomized,controlled clinical trial

This study provides preliminary evidence that risedronate not only preserves BMD but may also attenuate the loss of bone microarchitecture over 2 years during a time of accelerated bone loss in post-menopausal breast cancer survivors on aromatase inhibitors.IntroductionAccelerated bone loss and elevated fracture risk are associated with the use of aromatase inhibitors (AIs) in women with breast cancer. We previously reported that the oral bisphosphonate, risedronate, can maintain bone mineral density (BMD) in the hip and spine over 2-years in post-menopausal breast cancer survivors on AIs. In this study, we examined whether oral bisphosphonates can also preserve bone microarchitecture as measured by the trabecular bone score (TBS) in this population.MethodsThis 2-year randomized, double-blind, placebo-controlled trial included postmenopausal women over age 55 with breast cancer on an AI who had low bone mass. Participants provided informed consent and were randomized to risedronate 35 mg once weekly or placebo. We examined 12- and 24-month changes in spine TBS, analyzed using linear mixed models.ResultsOne-hundred and nine women with a mean age of 70.5 years were included in the analysis. In the placebo group, BMD declined at the spine and hip over the 24-month period but was preserved in the active treatment group (data previously reported). TBS declined in the placebo group by − 2.1% and − 2.3% at 12- and 24-months, respectively (p < 0.005). The TBS percent change in bisphosphonate-treated patients was − 0.9% and − 1.3% at 12 and 24-months but did not reach statistical significance (p = 0.24 and 0.14). The 12- and 24-month between-group differences were 0.9 (p = 0.38) and 0.8 (p = 0.44) percentage points. TBS change correlated with spine BMD changes in the placebo group at 12- and 24-months (r = 0.33 and 0.34, p < 0.01) but not in the active treatment group.ConclusionThe oral bisphosphonate risedronate preserves BMD and may attenuate loss of bone microarchitecture over 2 years during a time of accelerated bone loss in breast cancer survivors on AIs, but more definitive evidence is needed.     

Minodronic acid ameliorates vertebral bone strength by increasing bone mineral density in 9-month treatment of ovariectomized cynomolgus monkeys

The effect of treatment for 9 months with minodronic acid, a nitrogen-containing bisphosphonate, on vertebral mechanical strength was examined in ovariectomized (OVX) cynomolgus monkeys. Forty skeletally mature female monkeys were randomized into four OVX groups and one sham group (n = 8) based on lumbar bone mineral density (BMD). OVX animals were treated orally with 15 and 150 μg/kg QD of minodronic acid or 500 μg/kg QD alendronate as a reference drug. Measurements of bone turnover markers and lumbar BMD were conducted at 0, 4 and 8 months. Measurements of bone mechanical strength and minodronic acid concentration in vertebral bodies were also performed. OVX resulted in a decrease in lumbar BMD and an increase in bone turnover markers at 4 and 8 months, compared to the sham group, and the ultimate load on the lumbar vertebra was decreased in OVX animals. Minodronic acid and alendronate prevented the OVX-induced increase in bone turnover markers and decrease in lumbar BMD. Minodronic acid at 150 μg/kg increased the ultimate load on lumbar vertebra compared to untreated OVX animals. Regression analysis revealed that the ultimate load was correlated with lumbar BMD and bone mineral content (BMC), and most strongly with the increase in lumbar BMD and BMC over 8 months. In a separate analysis within the sham-OVX controls and minodronic acid and alendronate treatment groups, the ultimate loads were also correlated with BMD and BMC. The load-BMD (BMC) correlation in the minodronic acid group showed a trend for a shift to a higher load from the basal relationship in the sham-OVX controls. These results indicate that treatment with minodronic acid for 9 months increases vertebral mechanical strength in OVX monkeys, mainly by increasing BMD and BMC.     

Effectiveness of resistance training or jumping-exercise to increase bone mineral density in men with low bone mass: A 12-month randomized,clinical trial

PurposeTo examine the effects of 12 mo of resistance training (RT, 2 ×/wk, N = 19) or jump training (JUMP, 3 ×/wk, N = 19) on bone mineral density (BMD) and bone turnover markers (BTM) in physically active (≥ 4 h/wk) men (mean age: 44 ± 2 y; median: 44 y) with osteopenia of the hip or spine.MethodsParticipants rated pain and fatigue following each RT or JUMP session. All participants received supplemental calcium (1200 mg/d) and vitamin D (10 μg/d). BMD was measured at 0, 6, and 12 mo using DXA scans of the whole body (WB), total hip (TH) and lumbar spine (LS). BTM and 25 OHD were measured by ELISA. The effects of RT or JUMP on BMD and BTM were evaluated using 3x2 repeated measures ANOVA (time, group). This study was conducted in accordance with the Declaration of Helsinki and was approved by the University of Missouri IRB.ResultsAt baseline, 36 of 38 participants were vitamin D sufficient (25OHD > 50 nmol/L); at 12 mo, all participants were 25OHD sufficient. 25OHD did not differ between groups. WB and LS BMD significantly increased after 6 months of RT or JUMP and this increase was maintained at 12 mo; TH BMD increased only in RT. Osteocalcin increased significantly after 12 mo of RT or JUMP; CTx decreased significantly after 6 mo and returned to baseline concentrations at 12 mo in both RT and JUMP. Pain and fatigue ratings after RT or JUMP sessions were very low at 0, 6, and 12 mo.ConclusionRT or JUMP, which appeared safe and feasible, increased BMD of the whole body and lumbar spine, while RT also increased hip BMD, in moderately active, osteopenic men.     

Denosumab Densitometric Changes Assessed by Quantitative Computed Tomography at the Spine and Hip in Postmenopausal Women With Osteoporosis

FREEDOM was a phase 3 trial in 7808 women aged 60–90 yr with postmenopausal osteoporosis. Subjects received placebo or 60 mg denosumab subcutaneously every 6 mo for 3 yr in addition to daily calcium and vitamin D. Denosumab significantly decreased bone turnover; increased dual-energy X-ray absorptiometry (DXA) areal bone mineral density (aBMD); and significantly reduced new vertebral, nonvertebral, and hip fractures. In a subset of women (N = 209), lumbar spine, total hip, and femoral neck volumetric BMD (vBMD) were assessed by quantitative computed tomography at baseline and months 12, 24, and 36. Significant improvement from placebo and baseline was observed in aBMD and vBMD in the denosumab-treated subjects at all sites and time points measured. The vBMD difference from placebo reached 21.8%, 7.8%, and 5.9%, respectively, for the lumbar spine, total hip, and femoral neck at 36 mo (all p ≤ 0.0001). Compared with placebo and baseline, significant increases were also observed in bone mineral content (BMC) at the total hip (p < 0.0001) largely related to significant BMC improvement in the cortical compartment (p < 0.0001). These results supplement the data from DXA on the positive effect of denosumab on BMD in both the cortical and trabecular compartments.     

Bone mineral density changes following discontinuation of ronacaleret treatment: Off-treatment extension of a randomized,dose-finding phase II trial

ContextParathyroidectomy in patients with hyperparathyroidism can produce subsequent increases in bone mineral density (BMD). Ronacaleret, a selective calcium-sensing receptor antagonist that stimulates endogenous parathyroid hormone release, induced mild hyperparathyroidism.ObjectiveThe aim of this study is to evaluate whether BMD changes after cessation of ronacaleret treatment.DesignObservational, off-treatment, extension of a randomized, placebo-controlled, dose-ranging phase II trial.SettingFifteen academic centers in seven countries.PatientsPostmenopausal women with low BMD; 171 out of 569 women in the parent study were enrolled in the extension study.InterventionsSubjects were treated with ronacaleret 100 mg (n = 16), 200 mg (n = 38), 300 mg (n = 35), or 400 mg (n = 32) once daily, alendronate 70 mg (n = 17) once weekly, or matching placebo (n = 33) for 10–12 months; BMD was measured after discontinuation of ronacaleret or alendronate treatment.Main outcome measureMean percent change in lumbar spine areal BMD by dual-energy X-ray absorptiometry at 6–12 months after discontinuing ronacaleret or alendronate compared with the 10- to 12-month BMD measurement of the parent study.ResultsAt the lumbar spine, all doses of ronacaleret resulted in gains in BMD while on treatment. These increases in BMD were maintained or increased after discontinuation of ronacaleret. All doses of ronacaleret caused bone loss at the total hip while on active treatment. However, there was an attenuation of this loss in the off-treatment extension study.ConclusionThe gain in BMD at the lumbar spine was maintained post-treatment and the loss of BMD at the total hip was attenuated. We hypothesize that there may have been some bone remineralization after cessation of ronacaleret.     

Reduced physical activity corresponds with greater bone loss at the trabecular than the cortical bone sites in men

Previous research has been inconclusive as to whether high peak bone mineral density (BMD, g/cm²) resulting from previous physical activity is retained with reduced activity later in life. The aim of this 12-year longitudinal study was to investigate the association between BMD loss and reduced physical activity (h/wk) at trabecular and cortical bone sites in men. Three groups with a mean age of 17 years at baseline were investigated: i) 51 athletes who discontinued their active careers during the follow-up period (former athletes), ii) 16 athletes who were active throughout the follow-up period (active athletes), and iii) 25 controls. BMD loss at the hip, spine, and pelvis (mainly trabecular bone) was compared to BMD loss at femur, humerus, and legs (mainly cortical bone) during a 12-year follow-up period. Across the total follow-up period in the total cohort, reduced physical activity was more strongly associated with changes at trabecular BMD sites, i.e. hip, spine, and pelvis (B = 0.008–0.005 g/cm² per weekly hour physical activity (h), p < 0.001), than at cortical bone sites, i.e. humerus, legs (B = 0.002–0.003 g/cm²/h, p < 0.05), and femur (p > 0.05). At the final follow-up, former athletes showed higher BMD than controls only at the cortical bone sites of the humerus, legs, and femur (difference 0.05–0.10 g/cm², p < 0.05). In conclusion, this study indicates that predominantly trabecular bone is lost with reduced physical activity levels in young men. Benefits were still evident at the more cortical sites eight years after the discontinuation of an active sports career.     

Effect of immobilization,off-loading and zoledronic acid on bone mineral density in patients with acute Charcot neuroarthropathy: A prospective randomized trial

BackroundBisphosphonates are commonly used as an adjuvant in the management of acute Charcot neuroarthropathy (CNA), although the clinical efficacy of the treatment is controversial. The aim of the present study is to investigate the effect of immobilization and zoledronic acid on bone mineral density (BMD) changes during the treatment of acute CNA.MethodsThirty-five patients with acute midfoot CNA were randomly assigned to treatment with either zolendronic acid or placebo. BMD of the lumbar spine and both hips was measured at baseline and after six months of treatment.ResultsComparison between BMD at presentation and at 6 months demonstrated a significant fall in BMD in the placebo group at the CNA-affected femoral neck (?3.2%, p = 0.016) and in the CNA-free hip (?1.2%, p = 0.026). Conversely, a significant rise in BMD was observed in the zolendronic acid group at all measured areas of the CNA-free hip.Discussion and conclusionsImmobilization and off-loading does not lead to marked disuse osteoporosis in patients with acute CNA after 6 months of treatment. Treatment with zoledronic acid led to a statistically significant increase in hip BMD compared to placebo.     

Changes in bone mineral density in premenopausal women with rheumatoid arthritis during a two-year follow-up

ObjectiveTo ascertain changes in axial bone mineral in premenopausal women with severe rheumatoid arthritis (RA) treated with and without prednisolone (PRED), we conducted a two-year follow-up study of axial bone mineral density (BMD) and bone mineral content (BMC).MethodsPremenopausal RA women (n = 74) attending wards in the Rheumatism Foundation Hospital, Heinola, Finland were consecutively recruited for a follow-up study of BMD. BMD measurements in the lumbar spine and left proximal femur (femoral neck) were performed using dual X-ray absorptiometry at baseline and after two years. BMD is expressed as BMC per projectional area g/cm². The Larsen score of 0–100 was assessed at the check-ups. Two RA groups were analyzed: patients receiving prednisolone (n = 48), RA with PRED group and without prednisolone (n = 26), RA without PRED group. The control group (n = 43) comprised age-matched, premenopausal healthy women.ResultsThe patients in the RA with PRED group had lower BMD values than those in the RA without PRED group at commencement of follow-up. The mean weight-adjusted BMD percentage change in the lumbar spine to two years was −1.5% in the RA with PRED group, +0.6% in the RA without PRED group and −0.6% among the controls; a significant difference (P = 0.030) was found between the RA groups. The mean BMC percentage change to two years in the lumbar spine was −2.2% in the RA with PRED-group (P = 0.003), +0.0 in the RA without PRED-group and −0.6% in the control group. Accordingly, the mean weight-adjusted BMD percentage change in the femoral neck to two years was −2.6% in the RA with PRED group, +0.4% in the RA without PRED group and −0.9% among the controls; the difference between the RA groups being again significant (P = 0.049). The mean BMC percentage change to two years in the femoral neck was −1.9% (P = 0.006), −0.4% and −0.8%, respectively. Mean BMD decreased significantly in both lumbar spine (P = 0.002) and femoral neck (P < 0.001) only in the RA with PRED group. However, in spite of statistical findings above, when BMD is expressed as BMC per projectional area there was no statistically significant difference between the three groups in the change in BMC or projectional area in the lumbar spine or femoral neck. There was no significant correlation between the change in BMD in lumbar spine or femoral neck and the change in Larsen score among the RA groups.ConclusionsWe conclude that according to BMC, premenopausal RA women both with and without prednisolone treatment and controls lost bone statistically similarly. It seems that the role of RA itself in the multifactorial development of axial bone mass during the first decade of severe RA is not the most essential issue. We assume that this role will be less important with better treatment of RA than our patients received. The amount of bone loss during treatment with low-grade prednisolone remains controversial.     

Serum uric acid plays a protective role for bone loss in peri- and postmenopausal women: A longitudinal study

ObjectiveOxidative stress has been linked to osteoporosis. Serum uric acid (UA), a strong endogenous antioxidant, has been associated with higher bone mineral density (BMD), lower bone turnover and lower prevalence of fractures in a large cross-sectional study of men. Whether this relationship is present in women and how UA relates to changes in BMD longitudinally has not been examined.MethodsA sample of 356 peri- and postmenopausal women, mean age 60.5 years was studied. Each individual had baseline BMD and body composition measurements by dual energy x-ray absorptiometry (DXA) and at least one repeat measure, on average 9.7 years later. Annual rate of change in BMD (A%ΔBMD) was calculated. UA was measured at each DXA visit. Calciotropic hormones and bone turnover markers were measured at the final visit only.ResultsCross-sectional data analyses revealed that women with higher UA levels had significantly higher absolute BMD measures at all skeletal sites. These women also had higher measures of body weight and its components such as lean mass (LM) and fat mass (FM). Results of multiple regression analyses showed a positive association between UA and BMD that remained significant even after accounting for possible confounders including LM and FM. Regression analyses of the longitudinal BMD data demonstrated significant associations between serum UA levels and annual rates of change in BMD at all skeletal sites. After adjustment associations remained significant for lumbar spine, forearm and whole body BMD but not for hip BMD.ConclusionHigher serum UA levels appear to be protective for bone loss in peri- and postmenopausal women and this relationship is not affected by changes in body composition measures.     

Changes in bone mineral density after allogenic stem cell transplantation

ObjectiveOsteoporosis is a complication after allogenic stem cell transplantation (alloSCT). The purpose of this study was to assess changes in bone mineral density (BMD) 6 months and 3 years after alloSCT, as well as predictors of bone loss.MethodsA longitudinal, prospective, single-center study was conducted at Lille University Hospital between 2005 and 2016. Clinical, biological, radiologic (thoracic and lumbar spine) and densitometric (DXA) assessments were carried out at baseline (pre-transplant), 6 months and 3 years. Patients with myeloma were not included.ResultsTwo hundred and fifty-eight patients were included (144 men). Among them, 60.1% had leukemia and 65.8% of them, acute myeloid leukemia. At baseline, 6 months and 3 years, DXA-confirmed that osteoporosis was observed in 17%, 22.8% and 17.5% of the patients, respectively, mainly at the femoral neck. At baseline, 6 months and 3 years, 9 (8.5%), 53 (21.5%) and 38 (16.7%) patients, respectively, were receiving anti-osteoporotic treatment. From baseline to 6-month follow-up, BMD decreased significantly (p < 0.001) at the lumbar spine (?36 [95%CI; ?51 to ?20] mg/cm² of hydroxyapatite), femoral neck (?43 [95%CI; ?57 to ?29] mg/cm² of hydroxyapatite) and total hip (?53 [95%CI; ?68 to ?39] mg/cm² of hydroxyapatite). From 6-month to 3-year follow-up, a significant increase in BMD was observed at the lumbar spine only (+31 [95%CI; 20 to 42] mg/cm² of hydroxyapatite, p < 0.001). At all 3 sites, changes in BMD did not differ between patients treated or untreated by anti-osteoporotic treatment from 6-month to 3 year follow-up. Incident fractures were found in 4.1% and 5.7% of the patients at 6 months and 3 years, respectively. Between baseline and 6 months, bone loss at all 3 sites was associated with corticosteroid intake. At the total hip, 23.3% of the decrease in BMD from baseline to 6 months was due to an active hematological disease (p < 0.05), a bone marrow stem cells (p < 0.01) and a corticosteroid intake (p < 0.01).ConclusionOur study found evidence of bone fragility in alloSCT patients. Low BMD persisted at the hip 3 years after transplantation due to slower improvement at this site.     

Effect of vitamin D3 treatment on bone density in neurofibromatosis 1 patients: A retrospective clinical study

ObjectivesWe have previously demonstrated reduced bone density and an increased incidence of 25-hydroxy vitamin D₃ (25-OH D₃) deficiency in adults with neurofibromatosis 1 (NF1) compared to healthy controls. Vitamin D₃ is a cheap, safe, and effective supplement in the general population, but its value in NF1 patients has not been demonstrated. This study investigates the therapeutic potential of oral vitamin D₃ on bone mineral density (BMD) in NF1 patients with vitamin D₃ deficiency.MethodsWe measured serum 25-OH D₃, parathyroid hormone, calcium, and bone alkaline phosphatase concentrations, urinary deoxypyridinoline concentrations, and BMD in 35 adults with NF1. Nineteen patients received vitamin D₃ supplementation for 2 years, six patients received supplementation for 1 year and 10 patients received no supplementation. Supplementation was administered in a dose that maintained the serum 25-OH D₃ level above 30 μg/l. BMD was measured again at 1 and 2 years, and biochemical assessments of bone metabolism were measured at least every half year during therapy.ResultsTreated subjects had significantly reduced loss of BMD, as measured by T score at the hip (p = 0.011) and lumbar spine (p = 0.022). The effect on hip BMD was apparent at 1 year in comparison to baseline (p = 0.02) and was greater at 2 years in comparison to measurements at 1 year (p = 0.02).ConclusionsVitamin D₃ supplementation improves BMD in adult NF1 patients. Further studies are needed to elucidate the mechanisms responsible for reduced BMD in NF1 patients.