Increment In Bone Mineral Density Research Articles

PLS3 Mutations in X-Linked Osteoporosis: Clinical and Genetic Features in Five New Families.

Childhood-onset osteoporosis is a rare but clinically significant condition. Studies have shown pathogenic variants in more than 20 different genes as causative for childhood-onset primary osteoporosis. The X-chromosomal PLS3, encoding Plastin-3, is one of the more recently identified genes. In this study, we describe five new families from four different European countries with PLS3-related skeletal fragility. The index cases were all hemizygous males presenting with long bone and vertebral body compression fractures. All patients had low lumbar spine bone mineral density (BMD). The age at the first clinical fracture ranged from 1.5 to 13 years old. Three of the identified PLS3 variants were stop-gain variants and two were deletions involving either a part or all exons of the gene. In four families the variant was inherited from the mother. All heterozygous women reported here had normal BMD and no bone fractures. Four patients received bisphosphonate treatment with good results, showing a lumbar spine BMD increment and vertebral body reshaping after 10months to 2years of treatment. Our findings expand the genetic spectrum of PLS3-related osteoporosis. Our report also shows that early treatment with bisphosphonates may influence the disease course and reduce the progression of osteoporosis, highlighting the importance of early diagnosis for prompt intervention and appropriate genetic counseling.

Effect of a single dose of zoledronic acid on bone mineral density and trabecular bone score in Indian postmenopausal osteoporotic women with and without type 2 diabetes mellitus - A prospective cohort pilot study.

The objectives were to study the effect of a single dose of intravenous (IV) zoledronic acid (ZA) on changes in bone mineral density (BMD) (lumbar spine (LS), hip, & distal forearm), trabecular bone score (TBS) and bone turnover markers (BTMs) in postmenopausal osteoporotic women with and without diabetes over 12 months. Patients were divided into two groups: type 2 diabetes mellitus (T2DM) (n = 40) and non-DM (n = 40). Both groups received a single dose of 4 mg IV ZA at baseline. The BMD with TBS and BTMs (β-CTX, sclerostin, P1NP) were measured at baseline, six months, and 12 months. At baseline, BMD in all three sites was similar in both groups. T2DM patients were older and had lower BTMs than non-DM patients. The mean increase in LS-BMD (gram/cm2) at 12 months in T2DM and the non-DM group was 3.6 ± 4.7% and 6.2 ± 4.7 %, respectively (P = 0.01). However, the age adjusted mean difference in LS BMD increment between two groups at one year was - 2.86 % (-5.02% to -0.69%), P = 0.01. There was a comparable change in BMD at other two sites, BTMs, and TBS in both the groups over one year follow-up. The gain in the LS-BMD was significantly lower in T2DM group compared to non-DM subjects over 12 months after a single IV infusion of 4 mg ZA. The explanation for this could be low bone turnover in diabetes subjects at baseline.

Does chronic low-dose aspirin use benefit bone health? A cross-sectional study on patients with type 2 diabetes mellitus

IntroductionNumerous studies have reported the striking result that aspirin use is associated with higher bone mineral density (BMD), suggesting its potential as a population-wide osteoporosis prevention measure. Therefore, this study aimed to examine the impact of chronic low-dose aspirin use on bone remodeling biomarkers and BMD in an aging population.Materials and methodsBetween September and November of 2019, clinical data regarding the medication use, serum bone remodeling biomarkers, and BMD of 567 consecutively hospitalized patients, a minimum of 50 years old with type 2 diabetes mellitus (T2DM), were collected. The cross-sectional associations between chronic low-dose aspirin use and serum concentrations of bone remodeling biomarkers and BMD were estimated separately using linear regression. Potential confounding variables were controlled for, including age, sex, and comorbidities.ResultsLow-dose aspirin users had significantly lower serum bone alkaline phosphatase (BAP) concentrations than non-users (82.44 ± 28.03 U/L vs 90.71 ± 32.79 U/L, p = 0.025). On the other hand, low-dose aspirin users had insignificantly higher vertebral BMD (0.95 ± 0.19 vs 0.91 ± 0.21, p = 0.185), femoral neck BMD (0.80 ± 0.15 vs 0.78 ± 0.17, p = 0.309) and Ward’s triangle BMD (0.46 ± 0.14 vs 0.44 ± 0.13, p = 0.209), regardless of adjustment.ConclusionsThis cross-sectional study demonstrated that chronic use of low-dose aspirin was associated with significantly lower serum concentrations of BAP in hospitalized patients with T2DM. The mechanism causing the insignificantly higher BMD observed in chronic aspirin users in this study and the significant increments in BMD reported in previous studies requires further clarification in other clinical trials.

Effect of Teriparatide Versus Zoledronate on Posterior Lumbar Interbody Fusion in Postmenopausal Women with Osteoporosis

We evaluated the efficacy of teriparatide versus zoledronate on spinal fusion in osteoporotic patients after posterior lumbar interbody fusion (PLIF). Postmenopausal women with osteoporosis undergoing PLIF for degenerative spondylolisthesis were randomly assigned to receive either zoledronate or teriparatide. During the 2-year follow-up period, serial radiographs were used to determine fusion status and instrumentation-related sequelae (a composite of adjacent vertebral compressive fracture, instrumentation failure, and fusion failure). The bone mineral density (BMD) and Oswestry disability index (ODI) were also serially measured. Of the 77 patients, 36 were in the teriparatide group and 41 in the zoledronate group and had completed the 2-year follow-up assessments. Bony union had been achieved more frequently in the teriparatide group than in the zoledronate group at 6 months postoperatively (P < 0.05), although the overall rate of bone union was comparable between the 2 groups. The incidence of instrumentation-related sequelae was also comparable between the 2 groups (teriparatide vs. zoledronate group, 13.9% vs. 22.0%). Regarding antiosteoporosis, the BMD values had significantly improved in both groups at the last follow-up. The teriparatide group had attained more BMD increments at 12 months postoperatively than had the zoledronate group. Furthermore, the ODI had consistently decreased in both groups with a lower ODI in the teriparatide group than in the zoledronate group at 12 months postoperatively. Among postmenopausal women with osteoporosis, teriparatide showed superior bone union at 6 months and greater BMD improvement at 12 months after PLIF compared with zoledronate administration, although both resulted in similar overall effects on spinal fusion.

The Long-Term Effects of Growth Hormone Replacement on Bone Mineral Density and Trabecular Bone Score: Results of the 10-Year Prospective Follow-up.

There are only few studies concerning about long-term effect of growth hormone (GH) replacement therapy on bone mineral density and bone microstructure. To assess effect of GH replacement therapy on bone mineral density (BMD) and trabecular bone score (TBS) in adult GH deficient (AGHD) subjects over period of 10 years. From 2005 to 2018, a prospective study of AGHD patients was conducted in national referral center for treatment of GHD. All patients received subcutaneous recombinant human GH in an IGF 1-normalizing regimen once a day. Lumbar spine (L-spine) and total hip (TH) BMD using Hologic densitometers were measured at baseline and every two years during treatment with rhGH. TBS was derived from L1-L4 DXA using iNsight® software (Medimaps, France) at each time point. Periods of measurement were baseline, year 2; 4; 6; 8 and 10. In total, 63 patients (38 males, 25 females, mean age 25.1±16 years) were included in the study. After 10 years of GH treatment, IGF-1 significantly increased (~35 %), with greatest increase at year 2. During 10-year follow-up, L-spine BMD increased approximately of 7 % (NS). TH BMD increase of 11 % during follow-up (p=0.0003). The greatest increment of BMD was achieved at year 6 on both sites, L-spine (+6 %) and TH BMD (+13 %) (p<0.05). There was no significant change of TBS during whole follow-up. In this study, sustaining positive effect of GH replacement therapy on bone density in subjects with adult GH deficiency over 10 years of follow-up was observed. The study did not show effect on TBS, as indirect measure of trabecular bone microarchitecture.

Increased Bone Mineral Density in Male Patients With Idiopathic Hypogonadotropic Hypogonadism Who Undergo Sex Hormone Therapy: Findings From Cross-Sectional and Longitudinal Studies

ObjectiveThis retrospective observational study assessed the long-term impact of pulsatile gonadotropin-releasing hormone, combined gonadotropin, or testosterone replacement therapy on total hip, femoral, and lumbar bone mineral density (BMD) and Z-scores in adult men with idiopathic hypogonadotropic hypogonadism (IHH). MethodsIn the cross-sectional study, 69 patients were allocated to untreated (n = 42) and treated (n = 27) groups. The untreated group included IHH patients without hormone therapy history, while the treated group included age- and body mass index-matched patients who had received hormone therapy for at least 5 years. The longitudinal study included 53 IHH patients, and their hip and lumbar BMDs were measured several times during hormone therapy. We then evaluated the changes in their BMD. ResultsOur cross-sectional study showed that the treated group had a significantly higher BMD and Z-score for total hip, femoral neck, and lumbar spine (P < 0.001 for all) than the untreated group, and the average bone mass even reached the age-matched normal range. The prevalence of low BMD was 80.95% and 11.11% in untreated and treated groups, respectively. In the longitudinal study (N = 53), the total hip, femoral neck, and lumbar spine BMD gradually increased during treatment. The lumbar spine showed a greater increment in BMD compared with the total hip and femoral neck (P < 0.05). ConclusionSex hormone therapy improved hip and lumbar spine BMD and Z-scores in patients with IHH. The lumbar spine showed a greater improvement in BMD compared with the total hip and femoral neck.

The influence of lactation on BMD measurements and TBS: a 12-month follow-up study

To evaluate trabecular bone score (TBS) and bone mineral density (BMD) in postpartum women. This was a 12-month prospective cohort study with 40 lactating postpartum women and 44 non-pregnant women. The inclusion criteria were as follows: aged between 18 and 35 years old, an uncomplicated term (≥37 weeks) pregnancy with a single fetus, and no intention of becoming pregnant within 12 months. BMD measurements, including spine, hip, forearmand whole body, were performed by DXA at four different time points after delivery: (1) 1st month, (2) 3rd-4th month, (3) 6th-9th month, and (4) ≥ 12th month postpartum. BMD measurements showed a statistically significant decrease at spine (1.134 vs. 1.088 g/cm2, p < 0.01), femoral neck (0.988 vs. 0.946 g/cm2, p < 0.01), total femur (0.971 vs. 0.933 g/cm2, p < 0.01), and whole body (1.132 vs. 1.119 g/cm2, p = 0.03) at the 2nd assessment (peak of lactation). There was early spinal recovery after the 3rd assessment with complete recovery in all skeletal sites. Although it has had significant weight loss (67.3 vs. 63.2 kg, p < 0.01) and body mass index reduction (25.2 vs. 23.4, p < 0.01), there was significant increment of spine BMD (1.134 vs. 1.165 g/cm2, p < 0.01) after 12-month follow-up. The TBS did not change over time. Although lactation is associated with transient bone loss and body weight changes, the unchanged TBS could highlight a limited effectiveness in detecting dynamic bone properties in the first year postpartum.

Bone mineral density and osteoporosis in relation to all-cause and cause-specific mortality in NHANES: A population-based cohort study.

The majority of the published studies ascertaining the relationships between low bone mineral density (BMD) and mortality highlighted the elderly population with limited sample size. Our study aimed to ascertain the relationships in general population. This study ascertained the relationships between BMD levels in femur and lumbar spine with all-cause and cause-specific mortality in the National Health and Nutrition Examination Survey (NHANES) (n=15,076, mean age 48.6years). Cox proportional hazards models were adopted to calculate the hazard ratios (HR) and the corresponding 95% confidence intervals (CIs) for mortality. During a 6.8-year median follow-up, 1216 men and women in the cohort died. There was a higher risk of all-cause mortality among participants with osteoporosis compared with normal in the regions of total femur (HR=1.36, 95% CI=1.07-1.73), femur neck (HR=1.41, 95% CI=1.11-1.78), intertrochanter (HR=1.34, 95% CI=1.05-1.72), as well as overall (HR=1.36, 95% CI=1.09-1.69). Non-linear dose-response analyses showed a statistically significant L-shaped association for all-cause mortality with BMD increment in the regions of total femur, femur neck, trochanter, and intertrochanter. The protective role of higher BMD level in femur for decreased risk of cancer mortality and heart diseases mortality was more evident in male participants and female participants, respectively. In summary, our results revealed that maintaining normal BMD is critical to lower the risk of mortality. The association between higher BMD level in femur and decreased risk of cancer as well as heart diseases mortality varies by gender.

High Impact Exercise Improves Bone Microstructure and Strength in Growing Rats

Physical activity is beneficial for skeletal development. However, impact sports during adolescence, leading to bone growth retardation and/or bone quality improvement, remains unexplained. This study investigated the effects of in vivo low (LI), medium (MI), and high (HI) impact loadings applied during puberty on bone growth, morphometry and biomechanics using a rat model. 4-week old rats (n = 30) were divided into control, sham, LI, MI, and HI groups. The impact was applied on the right tibiae, 5 days/week for 8 weeks mimicking walking (450 µε), uphill running (850 µε) and jumping (1250 µε) conditions. Trabecular and cortical parameters were determined by micro-CT, bone growth rate by calcein labeling and toluidine blue staining followed by histomorphometry. Bio-mechanical properties were evaluated from bending tests. HI group reduced rat body weight and food consumption compared to shams. Bone growth rate also decreased in MI and HI groups despite developing thicker hypertrophic and proliferative zone heights. HI group showed significant increment in bone mineral density, trabecular thickness, cortical and total surface area. Ultimate load and stiffness were also increased in MI and HI groups. We conclude that impact loading during adolescence reduces bone growth moderately but improves bone quality and biomechanics at the end of the growing period.

Standard Versus Cyclic Teriparatide and Denosumab Treatment for Osteoporosis: A Randomized Trial.

In the absence of an intervening antiresorptive agent, cyclic administration of teriparatide does not increase bone mineral density (BMD) more than standard daily therapy. Because denosumab is a potent antiresorptive agent with a rapid off-effect, we hypothesized that it might be the optimal agent to help maximize bone gains with cyclic teriparatide. In this 3-year protocol, 70 postmenopausal women with osteoporosis were randomized to 18 months of teriparatide followed by 18 months of denosumab (standard) or three separate 12-month cycles of 6 months of teriparatide followed by 6 months of denosumab (cyclic). BMD (dual-energy X-ray absorptiometry [DXA]) measurements of lumbar spine (LS), total hip (TH), femoral neck (FN), and 1/3 radius (RAD) were performed every 6 months and total body bone mineral (TBBM) at 18 and 36 months. Baseline descriptive characteristics did not differ between groups except for a minimal difference in LS BMD but not T-score (mean age 65 years, mean LS T-score - 2.7). In the standard group, BMD increments at 36 months were: LS 16%, TH 4%, FN 3%, and TBBM 4.8% (all p < 0.001 versus baseline). In the cyclic group, 36-month BMD increments were similar: LS 12%, TH 4%, FN 4%, and TBBM 4.1% (all p < 0.001 versus baseline). At 36 months, the LS BMD increase with standard was slightly larger than with cyclic (p = 0.04), but at 18 months, in the cyclic group, there was no decline in RAD or TBBM (p = 0.007 and < 0.001, respectively, versus standard). Although the cyclic regimen did not improve BMD compared with standard at 36 months, there appeared to be a benefit at 18 months, especially in the highly cortical skeletal sites. This could be clinically relevant in patients at high imminent risk of fracture, particularly at nonvertebral sites. © 2019 American Society for Bone and Mineral Research. © 2019 American Society for Bone and Mineral Research.

Longitudinal changes in bone mineral density and trabecular bone score following yearly zoledronic acid infusion in postmenopausal osteoporosis-a retrospective-prospective study from southern India.

There is limited information available with regard to the impact of zoledronic acid treatment on bone mineral density (BMD) and trabecular bone score (TBS) in Indian postmenopausal women with osteoporosis. We studied the changes in BMD at femoral neck (FN), hip and lumbar spine (LS), and in TBS following yearly administration of zoledronic acid (ZA) in subjects with postmenopausal osteoporosis. This was a prospective-retrospective study which included subjects on follow-up after administration of yearly zoledronic acid, over the past 6years. Postmenopausal women with a T score of ≤ - 2.5 at any site, assessed by dual energy X-ray absorptiometry (DXA), were included. A total of 620 subjects had received ZA during the study period, 197 postmenopausal women were eligible, and follow-up data were available in 164 and 103 at 1st and 2nd follow-up yearly visits respectively. The mean (SD) age and BMI of the women were 63.2 (8.5) years and 25.6 (4.5)kg/m2 respectively. There was significant increment in LS BMD from baseline to the 1st and 2nd follow-up visits, respectively (mean (SD), 0.718 (0.116), 0.734 (0.104), 0.762 (0.127)g/cm2, p = 0.024). No decline in the BMD at FN and hip at first and second follow visit was found. The TBS scores (n = 90) on baseline and follow-up visits were 1.260 (±0.11), 1.256 (± 0.15), and 1.242 (± 0.17) (p value = 0.71). Lumbar spine BMD showed significant improvement with zoledronic acid treatment. No decline was noted in femoral neck BMD and TBS with treatment.

Role of Bisphosphonate Therapy in Patients with Osteopenia: A Systemic Review.

By contrast to clinical trials exploring osteoporosis, clinical trials specifically designed for the osteopenic population are limited. Thus, less clinical data are available regarding treatment benefits and cost-effectiveness of treating a patient population with a bone mass density in the osteopenic range (T-score between -1 and -2.5). In this article, we aimed to highlight this high-risk population with a low bone mass density (BMD) susceptible to high fracture risk by reviewing different national and international guidelines for treating osteopenia. The cost-effectiveness of the therapy for the above-mentioned patient population is also discussed. By reviewing different clinical trials, we have specifically highlighted the role of bisphosphonate therapy for fracture risk reduction and increment in bone mineral density (BMD) in patients with osteopenia.

Impaired residual renal function predicts denosumab-induced serum calcium decrement as well as increment of bone mineral density in non-severe renal insufficiency.

Although denosumab-induced hypocalcemia has been frequently observed in patients with chronic kidney disease (CKD) stages 4-5D being treated with denosumab for osteoporosis, few studies have assessed the risk factors for serum-corrected calcium (cCa) reductions in patients with non-severe renal insufficiency. This study assessed the risk factors for reduced cCa concentration following denosumab administration and analyzed factors predictive of changes in bone mineral density (BMD). Seventy-seven osteoporotic patients, not including those with CKD stages 4-5D, were treated with 60mg denosumab once every 6months. Biochemical parameters and BMD were analyzed from prior to the initial dose until 1month after the second dose. Following the first administration of denosumab, cCa levels decreased, reaching a minimum on day 7. Multiple linear regression analyses showed that baseline cCa, estimated glomerular filtration rate (eGFR) < 60mL/min/1.73m2, tartrate-resistant acid phosphatase-5b (TRACP-5b), and bone alkaline phosphatase (BAP) or pretreatment with antiresorptive agents were significant factors independently associated with the absolute reduction in cCa from baseline to day 7 (ΔcCa0-7days). ΔcCa0-7days after the second dose of denosumab was significantly lower than that after the first dose. After 6months of denosumab treatment, both LS-BMD and FN-BMD significantly increased from baseline. LS-BMD and FN-BMD correlated significantly with baseline TRACP-5b or BAP and eGFR, respectively. Both low eGFR and high bone turnover were independent risk factors for denosumab-induced cCa decrement, and for increases in BMD. Pretreatment with antiresorptive agents may reduce the risk of hypocalcemia.

The associations between the changes in serum inflammatory markers and bone mineral accrual in boys with overweight and obesity during pubertal maturation: a 3-year longitudinal study in Estonian boys.

This longitudinal study aims to identify the inflammatory markers that most strongly associate with pubertal bone mineral density (BMD) increment in boys with overweight and obesity (OWB). Twenty-six OWB and 29 normal-weight boys were followed yearly for 3years to measure changes in 12 serum inflammatory markers, BMD (by DXA), and apparent volumetric BMD. The OWB group was further divided into two subgroups according to their BMI gain during the 3-year period. Data through time points presented as slopes were used to calculate correlation coefficients to explore the possible relationships between variables of interest. In the whole study group, linear mixed effects (LME) models were also used. Increment in serum VEGF concentration was inversely associated with an increase in total body (TB) BMD (r = - 0.82, P = 0.02) and TB bone mineral content (BMC)/height (r = - 0.82, P = 0.02) in those OWB whose BMI gain was higher during pubertal years. In the whole study group, the LME model confirmed the inverse association between VEGF and TB BMC/height (P < 0.05). EGF was inversely associated with LS BMD and LS BMAD (P < 0.05), whereas there was a positive association between IL-8 and TB BMAD and between IFN-γ and LS BMD (P < 0.05). Lower increment in BMD in OWB with higher BMI gain is associated with increasing serum VEGF concentration during pubertal maturation. VEGF, EGF, IL-8, and IFN-γ are significantly associated with BMD during pubertal maturation in boys with different BMI values.

A 10–year follow−up of bone mineral density in HIV−infected youths receiving tenofovir disoproxil fumarate

BackgroundThe use of tenofovir disoproxil fumarate (TDF) has simplified the antiretroviral regimen for HIV−infected patients and improved their compliance with treatment, but it has been associated with decreased bone mineral density (BMD) in adult patients, and data in pediatric patients are debated. The aim of the current study was to assess the long−term effect of TDF on BMD in young patients. MethodsBMD was measured at the lumbar spine and in the whole skeleton in 26 HIV–infected youths (13 female and 13 male, aged 5 to 17 years at baseline). BMD was measured yearly for 10 years as part of standard care. BMD changes were compared with those calculated from 202 healthy subjects aged 3 to 24 years. FindingsAll patients had good control of the infection during the 10–year study. BMD measurements changed significantly (P < 0 ⋅ 0001) in HIV−infected youths. The mean annual BMD increment at the lumbar spine was 0 ⋅ 046 (0 ⋅ 006) g/cm2 and 0 ⋅ 042 (0 ⋅ 006) g/cm2 in males and females, respectively. The differences between the slopes of patients and healthy controls were not significant. The annual BMD increment of the whole skeleton was 0 ⋅ 030 (0 ⋅ 005) g/cm2 in males and 0 ⋅ 019 (0 ⋅ 004) g/cm2 in females. The slopes of BMD changes of patients and healthy controls did not differ significantly. InterpretationThese data indicate that treatment with a TDF−containing antiretroviral regimen does not impair BMD in young patients with HIV−infection. Larger studies are needed to confirm these results.

Extensive BMI Gain in Puberty is Associated with Lower Increments in Bone Mineral Density in Estonian Boys with Overweight and Obesity: A 3-Year Longitudinal Study

The aim of this 3-year prospective study was to examine changes in bone mineral characteristics during pubertal maturation in boys with different BMI values at the beginning of puberty and with different BMI increments during puberty. 26 boys with overweight and obesity (OWB) and 29 normal weight boys (NWB) were studied yearly for 3 years from the age of 11 years to measure the changes in different bone mineral characteristics. The OWB group was further divided into two subgroups according to extensive or non-extensive BMI increment during 3-year period. OWB had higher (P < 0.01) baseline total body (TB) bone mineral density (BMD), TB bone mineral content (BMC), TB BMC for height, lumbar spine (LS) BMD, and LS BMC compared to NWB. Throughout the study period, OWB gained more TB BMD (P = 0.0001), TB BMC (P = 0.0048), TB BMC for height (P = 0.0124), LS BMD (P = 0.0029), and LS BMC (P = 0.0022) compared to NWB. Also during the study period, TB BMD (P = 0.0065), TB BMC (P = 0.0141), TB BMC for height (P = 0.0199), LS BMD (P = 0.0066), LS apparent volumetric BMD (BMAD) (P = 0.0075), and LS BMC (P = 0.017) increased significantly less in those OWB whose BMI increased more extensively. Extensive BMI gain is associated with lower increments in bone mineral characteristics in boys with overweight and obesity. Unfavorable increment in total body fat mass and percentage during pubertal years could be one reason for that.

Impact of Calcium and Two Doses of Vitamin D on Bone Metabolism in the Elderly: A Randomized Controlled Trial.

The optimal dose of vitamin D to optimize bone metabolism in the elderly is unclear. We tested the hypothesis that vitamin D, at a dose higher than recommended by the Institute of Medicine (IOM), has a beneficial effect on bone remodeling and mass. In this double-blind trial we randomized 257 overweight elderly subjects to receive 1000 mg of elemental calcium citrate/day, and the daily equivalent of 3750 IU/day or 600 IU/day of vitamin D3 for 1 year. The subjects' mean age was 71 ± 4 years, body mass index 30 ± 4 kg/m2 , 55% were women, and 222 completed the 12-month follow-up. Mean serum 25 hydroxyvitamin D (25OHD) was 20 ng/mL, and rose to 26 ng/mL in the low-dose arm, and 36 ng/mL in the high-dose arm, at 1 year (p < 0.05). Plasma parathyroid hormone, osteocalcin, and C-terminal telopeptide (Cross Laps) levels decreased significantly by 20% to 22% in both arms, but there were no differences between the two groups for any variable, at 6 or 12 months, with the exception of serum calcitriol, which was higher in the high-dose group at 12 months. Bone mineral density (BMD) increased significantly at the total hip and lumbar spine, but not the femoral neck, in both study arms, whereas subtotal body BMD increased in the high-dose group only, at 1 year. However, there were no significant differences in percent change BMD between the two study arms at any skeletal site. Subjects with serum 25OHD <20 ng/mL and PTH level >76 pg/mL showed a trend for higher BMD increments at all skeletal sites, in the high-dose group, that reached significance at the hip. Adverse events were comparable in the two study arms. This controlled trial shows little additional benefit in vitamin D supplementation at a dose exceeding the IOM recommendation of 600 IU/day on BMD and bone markers, in overweight elderly individuals. © 2017 American Society for Bone and Mineral Research.

Relationship between baseline characteristics and response to risedronate treatment for osteoporosis: data from three Japanese phase III trials

SummaryWe evaluated the influence of baseline age, bone mineral density (BMD), and serum levels of vitamin D on the response to risedronate treatment. Risedronate consistently increased BMD, but our results suggest vitamin D supplementation may be necessary to achieve optimal treatment effect. Furthermore, early intervention may help prevent bone fractures.IntroductionWe aimed to investigate the influence of baseline age, BMD, and vitamin D insufficiency on the response to risedronate treatment.MethodsData regarding 1447 patients was obtained from the registries of three phase III clinical trials of risedronate. The response to treatment was expressed in terms of BMD increase and occurrence of new vertebral fractures. The patients were stratified by baseline values for age (<65, 65–72, and ≥72 years), lumbar spine BMD T-score (osteoporotic, <−2.5; and non-osteoporotic, ≥− 2.5), and serum levels of 25-hydroxyvitamin D (deficient, <21 ng/mL; and non-deficient, ≥21 ng/mL).ResultsRisedronate consistently increased lumbar spine BMD in all the groups, with similar percentage and absolute increments in all the age tertiles. The percentage, but not absolute, increment in BMD was significantly higher (p = 0.0003) in the osteoporotic than that in the non-osteoporotic patients (baseline). Of the 1330 patients whose baseline serum levels of 25-hydroxyvitamin D were available, 44.7% had vitamin D deficiency (<20 ng/mL), while 89.2% had insufficiency (<30 ng/mL). The percentage and absolute increments in BMD were lower (p < 0.05 and p < 0.01, respectively) in the vitamin D-deficient than those in the non-deficient patients. New vertebral fractures occurred in 1.5 and 0.8% of the osteoporotic and non-osteoporotic patients, respectively (end of the treatment).ConclusionsTherapeutic response in elderly patients is consistent, but early initiation of risedronate treatment may help prevent fractures. Risedronate-induced increase in BMD is lower in patients with vitamin D deficiency, suggesting that vitamin D supplementation is important to achieve optimal treatment response.

Effects of long-acting testosterone undecanoate on bone mineral density in middle-aged men with late-onset hypogonadism and metabolic syndrome: results from a 36 months controlled study

We evaluated the effects of long-term testosterone replacement therapy (TRT) on the bone mineral density (BMD) in obese patients with metabolic syndrome (MS) and late-onset hypogonadism (LOH). Sixty men (mean age 57 ± 10) with low serum testosterone (T < 320 ng/dL) and MS regardless the presence of osteoporosis were enrolled. Forty men received intramuscular T-undecanoate (TU) four times/year for 36 months and 20 age-matched hypogonadal men with MS in whom T treatment was contraindicated were used as controls. Hormonal, biochemical markers, vertebral and femoral BMD by dual-energy x-ray absorptiometry were measured. At baseline, overall patients had mild osteopenia (lumbar BMD= 0.891 ± 0.097 g/cm2; femoral BMD= 0.847 ± 0.117 g/cm2). TU induced a significant improvement of bone mass after 36 months (lumbar BMD = 1.053 ± 0.145 g/cm2; p < 0.002; femoral BMD = 0.989 ± 0.109; p < 0.003 g/cm2) with a 5%/year increase and a significant reduction in hs-CRP without changes in body mass index. A direct relationship between serum T and BMD increments at the lumbar (r2 = 0.66, p < 0.0001) and femoral (r2 = 0.52, p < 0.0001) sites was demonstrated. Study adherence was 50% without serious side effects. Long-term TRT in middle-aged men with LOH and MS determines a significant increase in both vertebral and femoral BMD related to increased serum T levels, probably independently from estradiol modifications.

Pamidronate and zoledronate effects in the increment of bone mineral density and histomorphometry in rats

To compare increment of bone mineral density (BMD) with pamidronate, zoledronate and the isolated effect of proteinous diet in undernourished oophorectomized and non-oophorectomized female rats, besides validating BMD's indexes. 60 young female Lewis rats were divided into five experimental groups and a control group, oophorectomized and non-oophorectomized. The administration of drugs were submitted to proteinous and aproteinous diets. The variables analyzed were weight, bone densitometry, histomorphometry and biochemical evolution. In weight evaluation, the first interval showed a statistically meaningful increase in oophorectomized sample. In densitometry evaluation, the first interval showed statistically meaningful decrease in four medicated groups and third showed a statistically meaningful increase in 2 non-oophorectomized groups. In laboratory evaluation, there were an increase of total proteins and globulin, decrease of alkaline phosphatase, phosphorus and calcium (except for the oophorectomized) in four medicated groups and increase of phosphorus and calcium in 2 not medicated groups. In histomorphometric evaluation, the oophorectomized groups had smaller increment of BMD. The pamidronate and zoledronate have shown effectives in the increment of BMD. The proteinous diet itself possesses therapeutic effect in BMD though not significant compared with medicated animals. The results of histomorphometry allow validating BMD's indexes in this experimental model.