Changes In BMD Research Articles

SAT-514 The Decrease in Serum Parathyroid Hormone on Vitamin D Treatment Is Similar When Comparing Increases in Serum Free or Total 25 Hydroxyvitamin D in White and Black Women

Background: Recent advances in measurement of total serum 25OHD (T25D) led to development of free 25OHD (F25D) assays. The free hormone hypothesis states that only F25D which is about 0.02% of T25D is available for conversion to the active metabolite 1,25(OH)2D, the rest is bound to D binding protein (DBP) and albumin. In a previous paper (J Int Med 2018 Aug 23 online)we did not find a change in BMD or bone markers compared to F25D or T25D. A one month vitamin D study reported F25D was more highly correlated than T25D with serum PTH. If confirmed then F25D measurement would be clinically important. Methods: In two 12 month vitamin D placebo/dosing studies in young, old white and black women, serum T25D, F25D and PTH were measured at baseline and 12 months. The main inclusion criteria was vitamin D insufficiency (Diasorin serum T25D ≤ 20ng/ml). Serum T25D was remeasured by LCMS and F25D was measured by Elisa (Future Diagnostics). Serum PTH was measured by immunoassay (Diasorin). Group means were compared by t-test. Linear regression was used to assess percent change in T25D and F25D on percent change in PTH, accounting for age (young, old), race (Caucasians, African Americans) and interactions. Results: In the older women, there were 109 Caucasians and 79 African Americans with baseline measurements of F25D, T25D and PTH. Mean age (± SD) was 69 (± 7.3) years. In the younger women, there were 81 Caucasians and 31 African Americans, mean age 37 (± 5.6) years. In older women, serum T25D was similar in black compared to white women 18.70(±5.57) and 19.63(±5.19) ng/ml, p=0.24. Serum F25D was lower in older African Americans compared to Caucasians 3.38(±1.21) vs 3.73(±1.39) pg/mL (p=0.075). In younger women T25D was significantly lower in blacks 14.33(±4.13) compared to 22.09 (±5.45)ng/ml in whites, p<0.001. F25D was lower in blacks 3.55(±1.17) versus 4.64(±1.25) pg/ml p<0.001. Baseline mean serum PTH was higher in the older black women 44(±21) compared to whites 38 (±14)pg/ml (p=0.03). In young black women serum PTH was higher 44(±18) than white women 31(±10)(p<0.01). Serum PTH decreased on vitamin D. The decrease in PTH compared to levels of serum F25D was similar in young and old, black and white women. The decrease in PTH was 6% for each 1% increase in F25D. The slope for the regression of PTH on serum T25D was steeper in blacks than whites (p<0.01) but did not differ by age. The percent decrease in PTH was 13% in blacks and 5% in whites for each 1% increase in T25D. Summary: The percent decrease in serum PTH after vitamin D was related to increasing free and total 25D in young and old, black and white women. However, black women showed a significantly larger decrease in PTH with T25D, possibly because of more secondary hyperparathyroidism. Because the parathyroid gland has the megalin and cubilin receptors mechanism for uptake of DBP it may not be unexpected that the correlations between serum PTH and free and total 25(OH)D are so similar.

SUN-LB075 Effects of Pegvisomant and Pasireotide LAR on Incidence of Vertebral Fractures in Patients with Acromegaly Resistant to Treatment with First-Line Somatostatin Analogs

Purpose: Osteopathy is an emerging complication of acromegaly characterized by increased bone turnover, deterioration in bone microarchitecture and high risk of vertebral fractures (VFs). In somatostatin analog (SSA)- resistant patients (pts), Pegvisomant (PegV) and Pasireotide LAR (Pasi) are used for acromegaly treatment, but their effect on skeletal health is still not defined. Methods: In a longitudinal international multicenter study, we evaluated incidence of radiological VFs in 55 pts (29F/26M), mean age 44.1 yrs (SD: 17) with acromegaly resistant to first line SSA. Results: At the study entry, prevalent VFs (lumbar, thoracic) were identified in 23 pts (41.8%): 42 mild and 3 moderate (Genant score) VF. Mean spine Z-score was -0.4 (-0.6 in PegV, -0.2 in Pasi group, respectively; p=0.49). Biochemical acromegaly control was reached in 22 / 31 pts on Peg-V (71%) and in 16/24 pts on Pasi (66.7%). During the follow-up (mean 89.9 months for PegV group and 50.5 months for Pasi group), incident VFs were detected in 16 pts (29.1%). Occurrence of incident VFs was associated with the presence of pre-existing VFs (p=0.009), persistence of active acromegaly (p=0.009) and with higher median value of serum IGF-I during follow-up (p=0.04). There were no significant differences in age, gender, initial treatment choice and changes in lumbar spine BMD. Incident VFs occurred in 7/9 pts not contolled on Peg-V and 2/8 pts not controlled on Pasi. Among pts with active disease at last visit, incident VFs occurred less frequently in pts on treatment with Pasi (25%) compared to Peg-V (77.8%), p=0.03, independently of the IGF-I values (p=0.9). In pts who reached acromegaly biochemical control, 5/17 (22.7%) on Peg-V and 2/14 (12.5%) pts on Pasi had incident VFs, p=0.4. In pts on Peg-V, factors associated with incident VFs during follow-up were persistence of active acromegaly and higher values of IGF-I (median IGF x ULN: 0.5 IQR:1.8 vs 2.6 IQR: 2.2 p=0.02). In pts treated with Pasi, we did not find any factors associated with incident VFs. Furthermore, in pts with biochemically controlled acromegaly, no factor was associated with incident VFs which occurred less frequently in pts treated with Pasi. Conclusion: Our data confirm that active acromegaly is the main determinant of VFs and show for the first time that pts with biochemically active disease treated with Pasi had lower risk of incident VFs vs those treated with Peg-V. Conversely, no significant drug-related differences in incident VFs in pts with controlled acromegaly were observed. Additional studies on larger populations and with longer follow-up are needed to confirm our data and disclose the mechanisms underlying our findings. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

Effect of denosumab on trabecular bone score in de novo kidney transplant recipients.

Kidney transplant recipients (KTR) are at risk to lose bone mass. The trabecular bone score (TBS) represents a recently developed parameter of lumbar spine trabecular bone texture that correlates with the occurrence of fractures. We analysed the 1-year changes in TBS in 44 de novo KTR that were randomized 1:1 to denosumab or no treatment. TBS was derived from dual energy X-ray absorptiometry and was correlated with 1-year areal bone mineral density (aBMD) changes at the lumbar spine and total hip. Correlations were also performed with parameters of peripheral bone microarchitecture and bone strength at the distal tibia and distal radius, as assessed by high-resolution peripheral quantitative computed tomography (HRpQCT) and micro-finite element analysis. The baseline TBS in KTR amounted to 1.312 ± 0.101, which is lower than the TBS of an age-matched normal control population (range 1.364-1.471). The TBS correlated positively with aBMD at the lumbar spine (Spearman's ρ = 0.56; P < 0.001) and total hip (ρ = 0.33; P < 0.05). The baseline TBS also correlated with HRpQCT-derived total (ρ = 0.49; P < 0.05) and trabecular volumetric BMD (ρ = 0.57; P < 0.01) and trabecular separation (ρ = -0.46; P < 0.05) at the tibia. Denosumab treatment led to an increase in TBS, paralleling the BMD changes at the lumbar spine. The TBS is a useful additional score of bone health, which may help to better define fracture risk. Treatment with denosumab led to improved trabecular bone texture in de novo KTR in addition to its beneficial effect on BMD.

Physical activity modifies the effect of calcium supplements on bone loss in perimenopausal and postmenopausal women: subgroup analysis of a randomized controlled trial.

Physical exercise can potentially modify bone metabolism. Here we aimed to determine whether the effect of calcium supplements on bone metabolism is modified by physical activity (PA) through a subgroup analysis of a randomized, double-blind, placebo-controlled trial. The trial was conducted over the course of 2years, and participants were 450 healthy women between 50 and 75years of age who were randomly assigned to three equally-sized (N = 150 each) groups (500mg calcium, 250mg calcium, and placebo). Levels of PA at baseline were evaluated by quantifying moderate (4 METs) and vigorous (6 METs) activities based on a 7-day activity recall, and the total MET-hours per week was calculated. Follow-up BMD examinations were conducted 2years later. Two-year changes in BMD were compared between the intention-to-treat higher PA subgroup (≥ 10 MET-hours/week) and the lower PA subgroup (< 10 MET-hours/week). Of the 450 participants, 418 underwent follow-up BMD measurements. Regarding the lower PA subgroup, spinal BMD in the 500mg/day calcium supplement group decreased significantly less (- 0.029g/cm2, P = 0.042) than in the placebo group (- 0.045g/cm2), and femoral neck BMD in the 500mg/day calcium supplement group decreased significantly less (- 0.027g/cm2, P = 0.049) than in the placebo group (- 0.038g/cm2). In contrast, changes in neither spinal nor femoral neck BMD significantly differed between the three treatment groups in the higher PA subgroup. PA is a favorable effect modifier of the association between calcium intake and bone loss in perimenopausal and postmenopausal women with low calcium intake. UMIN000001176.

Effects of Denosumab and Alendronate on Bone Health and Vascular Function in Hemodialysis Patients: A Randomized, Controlled Trial.

Mineral and bone disorders including osteoporosis are common in dialysis patients and contribute to increased morbimortality. However, whether denosumab and alendronate are effective and safe treatments in hemodialysis patients is not known. Thus, we conducted a prospective, three-center study of 48 hemodialysis patients who were diagnosed as having osteoporosis and had not received anti-osteoporotic agents previously. Participants were randomized to either denosumab or intravenous alendronate, and all subjects received elemental calcium and calcitriol during the initial 2 weeks. The primary endpoint was the percent change in lumbar spine bone mineral density (LSBMD) at 12 months of treatment. The secondary endpoints included the following: change in BMD at other sites; change of serum bone turnover markers (BTM), coronary artery calcium score (CACS), ankle-brachial pressure index (ABI), brachial-ankle pulse wave velocity (baPWV), flow mediated dilation (FMD), and intima-media thickness at the carotid artery (CA-IMT); change from day 0 to day 14 in serum levels of Ca and P; time course of serum calcium (Ca), phosphorus (P), and intact parathyroid hormone (i-PTH); new fractures; and adverse events. Initial supplementation with elemental calcium and calcitriol markedly ameliorated the decrease of serum corrected calcium (cCa) levels induced by denosumab during the first 2 weeks, whereas serum cCa levels in the alendronate group were increased. Denosumab and alendronate markedly decreased serum levels of BTM and increased LSBMD at 12 months compared with baseline. However, no significant differences were found in the changes in LSBMD between the two groups. The serum cCa, P, and i-PTH levels in the two groups were maintained within the appropriate range. In contrast to the anti-osteoporotic effects, no significant differences after 12 months of treatment were found in the CACS, CA-IMT, ABI, baPWV, and FMD compared with pretreatment in both groups. Denosumab and alendronate treatment improved LSBMD, reduced BTM, and appeared to be safe in hemodialysis patients with osteoporosis. © 2019 American Society for Bone and Mineral Research.

Treatment with zoledronic acid subsequent to odanacatib prevents bone loss in postmenopausal women with osteoporosis.

The development of odanacatib (ODN), a cathepsin K inhibitor, for treatment of osteoporosis was discontinued due to an increased risk of cardiovascular events. As the treatment is considered reversible, participants from the LOFT trial in Aarhus, Denmark, were offered treatment with zoledronic acid (ZOL). Sixty-seven postmenopausal women were treated with ZOL 5mg and followed for 12months. Of these, 39 had received ODN for 7years and 28 had received placebo for 5years and ODN for 2years. Bone turnover markers (BTM) were measured 3, 6, and 12months after ZOL, and DXA of spine and hip were performed at time of ZOL treatment and after 12months. Within the entire study population, BMD at the lumbar spine increased by 2.8 ± 0.9% (mean ± SEM) (p < 0.01) from baseline to month 12. There was no significant change in BMD at the total hip (p = 0.17) or femoral neck (p = 0.39). There was no difference in the changes in BMD from baseline to 12months between the two groups at any site (p ≥ 0.20 for all). CTX increased by 107 ± 9% (p < 0.001), PINP by 102 ± 16% (p < 0.001), osteocalcin by 32 ± 6% (p = 0.001) and BSAP by 79 ± 37% (p = 0.001) between 3 and 12months after ZOL. At month 12, BTM were still within the premenopausal reference range. S-25-hydroxyvitamin D increased (p = 0.059), while PTH (p = 0.007) and eGFR (p = 0.014) decreased during the year following ZOL administration. Treatment with ZOL 5mg maintained BTMs in the premenopausal range and prevented bone loss in women previously treated with ODN.

Bone turnover markers to explain changes in lumbar spine BMD with abaloparatide and teriparatide: results from ACTIVE

SummaryEarly PINP changes correlate with 18-month lumbar spine BMD changes and the correlation was greater with abaloparatide versus teriparatide. The uncoupling index was similar between the two agents.IntroductionWe evaluated the relationship between early PINP changes and subsequent changes in spine BMD following abaloparatide and teriparatide treatments. We also explored the use of an “uncoupling index” (UI), the balance between bone formation and bone resorption, which we hypothesised would be similar in response to these treatment groups.MethodsBlood samples were taken for measurement of bone turnover markers (BTMs) s-PINP and s-CTX at baseline, 1, 3, 6, 12, and 18 months from 189 abaloparatide patients and 227 teriparatide patients randomly selected from all participants who completed the study. BMD was measured by DXA at baseline, 6, 12, and 18 months. Correlations were calculated between log ratio of BTMs from baseline to 3 months and percent change from baseline in BMD at 18 months. A UI was calculated using log transformation and subtraction of the standard deviate for s-CTX from the standard deviate for s-PINP for each patient.ResultsEarly BTM changes were associated with subsequent BMD changes for both treatments. Pearson correlations for the log ratio of PINP over baseline at 3 months and BMD percent change from baseline at 18 months were larger (P < 0.0001) with abaloparatide (r = 0.561) than teriparatide (r = 0.198). The mean UI at 1 month was greater for abaloparatide versus teriparatide (1.743 and 1.493, respectively; P = 0.03) but was similar at 3 months or later time points.ConclusionsEarly s-PINP changes correlate with percentage change in lumbar spine BMD 18 months after treatment with both abaloparatide and teriparatide, though the correlation with abaloparatide was greater. The UI was similar between abaloparatide and teriparatide suggesting that the balance between formation and resorption markers was similar.

Serum Periostin Level is not a Predictor of Early Stage Bone Loss in Chinese Postmenopausal Women.

Postmenopausal osteoporosis (PMOP) is one of the main threats to the health of women, which makes the early detection of bone loss vital. Many studies were carried out dedicated to finding new parameters and improving the discovery rate of early stage bone loss in postmenopausal women. Periostin is a newly discovered secreted protein that has been reported to participate in the processes of many agerelated diseases including osteoporosis. But the potential of serum periostin being a predictive marker of early stage bone loss remains to be determined. Two hundred thirty-seven Chinese postmenopausal women from the patients of General Hospital of Southern Theater Command of People's Liberation Army were included as the subjects of this baseline study. Serum periostin level, BMD, the serum levels of a series of bone turnover markers (P1NP, β-CTx and N-MID Osteo-calcin) and serum PTH level were measured. The follow-up study included 81 subjects with baseline BMD T-score ≥ -1.0 SD. BMD data at one year after baseline was available for all 81 subjects. The changes of BMD in different quartiles of serum periostin level were investigated. Serum periostin level was correlated with age but no matter whether adjusted by age there were no significant correlations between serum periostin levels and BMD, PTH, P1NP, β-CTx, and N-MID-OT levels at baseline. There were no differences in serum periostin level between women with normal and abnormal BMD T-scores (p = 0.89). BMD data at one year after baseline indicated that the femur neck BMC and T-score became lower in women with higher baseline serum periostin (3/4 and 4/4 in quartiles, p = 0.025, p < 0.001, respectively). Serum periostin is not a predictor of early stage bone loss in Chinese postmenopausal women. However, a downtrend of femur neck BMC was found in women who had a higher baseline serum periostin level at the one-year follow-up bone mineral densitometry, which suggests that the exact association between periostin, bone turnover, and fracture risk are worth further research and long-term clinical follow-up study.

Bone protection for early menopausal women in China: standard or half-dose estrogen with progestin? A one-year prospective randomized trail

The aim of the study is to compare the bone sparing effect of half-dose with standard-dose conjugated equine estrogen (CEE) combined with progestin. A total of 123 participants were administrated with 0.625 mg of CEE and 100 mg of micronized progesterone (MP) in group A, 0.3 mg of CEE and 100 mg of MP in group B, 0.625 mg of CEE and 10 mg of dydrogesterone (DDG) in group C for one year. Percent changes from baseline in BMD at lumbar spine and fracture rate were primary outcomes. Secondary endpoints included changes of BMD at femoral neck, total hip and arm, bone markers (alkaline phosphatase, calcium and phosphorus), serum alanine aminotransferase (ALT) and endometrial thickness. No fractures occurred during the treatment. Standard dose of CEE leads to significant changes in lumbar spine and arm. The 3.78% growth of BMD at femoral neck in group C marked a statistically difference. There was no statistically remarkable bone loss at hip in all three groups. Bone turnover markers and ALT significantly decreased from basic values. Endometrium thickened more with traditional dose of CEE. Both the half and standard dose CEE are effective in BMD preservation among early menopausal women with subtle side effects. Low-dose estrogen is less efficacious than traditional one.

Long-term effects of inhaled corticosteroids on bone mineral density in older women with asthma or COPD: a registry-based cohort study.

This study evaluated the impact of long-term ICS therapy on bone loss in older women with asthma or chronic obstructive pulmonary disease (COPD). We used a population-based bone densitometry registry linked with administrative health data covering the province of Manitoba, Canada (1999-2013), to identify women aged > 40years who had diagnosed asthma or COPD. ICS exposure was defined as cumulative dispensed days and medication possession ratio (MPR). Associations were examined both cross-sectionally and longitudinally, and results were covariate adjusted. Among 6561 women with asthma and/or COPD (mean age 65years [SD = 11]), compared to no ICS treatment, those in the highest tertile of prior ICS use (≥ 720days) had lower BMD at the femoral neck (- 0.09 T-score, 95% CI - 0.16, - 0.02) and total hip (- 0.14 T-score, 95% CI - 0.22, - 0.05), but not at the lumbar spine. Over a mean of 5years of follow-up, the highest tertile of ICS exposure (MPR > 0.5) was associated with a - 0.02 SD/year (95% CI - 0.04, - 0.01) greater decline in total hip BMD relative to non-users, with no significant effect at the femoral neck or lumbar spine. Middle and lower tertiles of ICS use were not associated with baseline or longitudinal change in BMD. The highest tertile of ICS use was associated with a slightly lower hip BMD at baseline and slightly greater reduction in total hip BMD over time in older women with asthma or COPD. No adverse effects on BMD were seen from low to moderate ICS exposure.

Abaloparatide, a novel osteoanabolic PTHrP analog, increases cortical and trabecular bone mass and architecture in orchiectomized rats by increasing bone formation without increasing bone resorption.

Male osteoporosis can occur with advanced age and with hypogonadism, with increased bone resorption and/or inadequate bone formation contributing to reduced bone mass and increased fracture risk. Abaloparatide is a selective PTH receptor agonist that increases bone formation and bone mass in postmenopausal women with osteoporosis and in estrogen-deficient animals. The current study evaluated the effects of abaloparatide in orchiectomized (ORX) rats, a model of male osteoporosis. Four-month-old Sprague-Dawley rats underwent ORX or sham surgery; 8 weeks later the ORX groups exhibited relative osteopenia vs sham controls, based on dual X-ray absorptiometry (DXA) and/or peripheral quantitative computed tomography (pQCT) assessments at the total body, lumbar spine, femur, and tibia. ORX rats (n = 10/group) were then injected daily (s.c.) for 8 weeks with vehicle or abaloparatide at 5 (ABL5) or 25 μg/kg/d (ABL25). Sham controls (n = 10) received s.c. vehicle. DXA and pQCT showed that one or both abaloparatide groups gained more areal and volumetric BMD at all sites analyzed compared with vehicle controls, leading to substantial or complete reversal of ORX-induced BMD deficits. pQCT also indicated greater gains in tibial cortical thickness in both abaloparatide groups versus vehicle controls. Tibial bone histomorphometry showed greater trabecular bone formation and bone volume and improved micro-architecture with abaloparatide, with no increase in osteoclasts. Abaloparatide also led to significant improvements in the balance of biochemical bone formation markers versus bone resorption markers, which correlated with BMD changes. These findings suggest that abaloparatide may have therapeutic benefits in men with osteoporosis.

Natural history of mineral metabolism, bone turnover and bone mineral density in de novo renal transplant recipients treated with a steroid minimization immunosuppressive protocol.

The skeletal effects of renal transplantation are not completely understood, especially in patients managed with a steroid minimization immunosuppressive protocol and long term. We enrolled 69 adult transplant recipients (39 males; ages 51.1 ± 12.2 years), free of antiresorptive therapy and managed with a steroid minimization immunosuppressive protocol, into a 5-year prospective observational study to evaluate changes in areal bone mineral density (aBMD), mineral metabolism and bone remodelling. Dual energy X-ray absorptiometry, laboratory parameters of mineral metabolism (including parathyroid hormone, sclerostin and fibroblast growth factor 23) and non-renal cleared bone turnover markers (BTMs) (bone-specific alkaline phosphatase, trimeric N-terminal propeptide and tartrate-resistant acid phosphatase 5b) were assessed at baseline and 1 and 5 years post-transplantation. The mean cumulative methylprednisolone exposure at 1 and 5 years amounted to 2.5 ± 0.8 and 5.8 ± 3.3 g, respectively. Overall, bone remodelling activity decreased after transplantation. Post-transplant aBMD changes were minimal and were significant only in the ultradistal radius during the first post-operative year {median -2.2% [interquartile range (IQR) -5.9-1.2] decline, P = 0.01} and in the lumbar spine between Years 1 and 5 [median 1.6% (IQR -3.2-7.0) increase, P = 0.009]. BTMs, as opposed to mineral metabolism parameters and cumulative corticosteroid exposure, associated with aBMD changes, both in the early and late post-transplant period. Most notably, aBMD changes inversely associated with bone remodelling changes. In summary, in de novo renal transplant recipients treated with a steroid minimization immunosuppressive protocol, BMD changes are limited, highly variable and related to remodelling activity rather than corticosteroid exposure.

Vigorous physical activity patterns affect bone growth during early puberty in boys.

The main purpose of the study was to analyze the effects of different patterns of vigorous physical activity (VPA) on bone development. One-week accelerometry registers and dual-energy X-ray absorptiometry scans at the whole body, hip, and lumbar spine of 140 healthy male adolescents (11-13years, at baseline) were performed twice with a 1-year interval between measurements. Four patterns of VPA evolution ("low-low," "low-high," "high-low," and "high-high") and three patterns of bone growth ("optimal," "mean," and "reduced") were defined according to the median participation in VPA and a cluster analysis of the longitudinal changes in BMC and BMD in all sites measured, respectively. Bone mineral parameters were adjusted for skeletal age and body weight prior to statistical comparison among groups. Participants in the "low-high" group had greater adjusted BMD increases at both the femoral neck and lumbar spine when compared to the "low-low" group (estimated mean (95% CI) 0.066 (0.047-0.085) vs. 0.034 (0.021-0.047) g/cm2 and 0.074 (0.054-0.093) vs. 0.049 (0.035-0.062) g/cm2 respectively, both p < 0.05). Femoral neck BMD adjusted increase was also different between the "high-high" and the "high-low" groups (0.053 (0.041-0.066) vs. 0.030 (0.011-0.049) g/cm2, p < 0.05). Additionally, a higher percentage of "optimal" growth was found in the "low-high" group than in the "low-low" and "high-low" categories (36.3, 12.5 and 13.6% respectively, p < 0.05). Engaging in VPA as well as maintaining high levels of VPA during puberty is associated with greater gains in bone mass, which can have an impact in future bone health.

Association between SOST gene polymorphisms and response to alendronate treatment in postmenopausal Chinese women with low bone mineral density.

The aim of this study was to explore the allelic association between SOST polymorphisms and the variance of clinical effects of alendronate in postmenopausal Chinese women with osteoporosis or osteopenia. In the study, 500 postmenopausal women in Shanghai area with osteoporosis or osteopenia were included. All participants were treated with weekly oral alendronate 70 mg, daily calcium 600 mg and vitamin D 125 IU for 12 months. Nine tagging single-nucleotide polymorphisms (SNPs) in SOST gene were genotyped. Bone mineral density of lumbar spine (L1-L4), left femoral neck and total hip were measured at baseline and after 1 year of treatment, respectively. In the study, 450 subjects completed the 1-year follow-up. The rs865429 was significantly associated with the % change of BMD at the femoral neck (P = 0.007). GG carriers seemed to be at an advantage after treatment of alendronate. Compared with AG and AA heterozygote, GG homozygote had the highest % change of BMD (3.100 ± 2.899%) at femoral neck. The odds ratio (95% confidence) of GG homozygote to be responders at femoral neck was 1.921 (1.211-3.048). Two haplotypes GG and AC constituted by rs865429 and rs851057 were associated with the % change of BMD at femoral neck and total hip, respectively. Therefore, the common variation of SOST gene contribute to the therapeutic response to alendronate treatment in Chinese women with osteoporosis or osteopenia.

The estrogen receptor 1 gene affects bone mineral density and osteoporosis treatment efficiency in Slovak postmenopausal women

BackgroundThe study investigated the associations of rs9340799:A > G (XbaI) and rs2234693:T > C (PvuII) polymorphisms in the estrogen receptor 1 gene (ESR1) with femoral neck (BMD-FN) and lumbar spine bone mineral density (BMD-LS), biochemical markers of bone turnover, calcium and phosphate levels, fracture prevalence, and a response to two types of anti-osteoporotic therapy in postmenopausal women from southern Slovakia.MethodsWe analysed 343 postmenopausal Slovak women (62.40 ± 0.46 years). The influence of rs9340799 (AA vs. AG + GG) and rs2234693 (TT vs. TC + CC) genotypes on BMD and biochemical markers was evaluated by covariance analysis adjusted for age and BMI. Binary logistic regression was used to evaluate the genotype effect on fracture prevalence. Pharmacogenetic part of the study included women who received a regular therapy of HT (17ß estradiol with progesterone; 1 mg/day for both; N = 76) or SERMs/raloxifene (60 mg/day; N = 64) during 48 months. The genotype-based BMD change was assessed by variance analysis for repeated measurements.ResultsWomen with AA genotype of rs9340799 had higher BMD-FN (+ 0.12 ± 0.57 of T-score) and BMD-LS (+ 0.17 ± 0.08 of T-score) in comparison with AG + GG. The rs2234693 polymorphism did not affect any of the monitored parameters. No effect of any ESR1 polymorphisms was found on fracture prevalence. Both types of anti-osteoporotic therapy had a positive effect on BMD improvement in FN and LS sites. Considering the effect of the ESR1 gene within the HT, the subjects with rs9340799/AA genotype showed worse response than those with GG genotype (− 0.26 ± 0.10 of BMD-FN T-score; − 0.35 ± 0.10 of BMD-LS T-score) and also with AG genotype (− 0.22 ± 0.08 of BMD-LS T-score). The rs2234693/TT genotype responded poorer in BMD-LS in comparison with TC (− 0.22 ± 0.08 of T-score) and CC (− 0.35 ± 0.09 of T-score). The effect of the ESR1 gene on raloxifene therapy was reported only in BMD-LS. Subjects with rs9340799/AA genotype had a − 0.30 ± 0.11 of T-score worse response compared to AG genotype. The rs2234693/TT genotype showed − 0.39 ± 0.11 and − 0.46 ± 0.15 lower T-scores in comparison with TC and CC genotypes, respectively.ConclusionsThe rs9340799 polymorphism may contribute to decreased BMD in postmenopausal women from southern Slovakia; however, this is not related to higher fracture prevalence. Concurrently, both polymorphisms affected a response to analysed anti-osteoporotic therapies.

Bone mass preservation with high-dose cholecalciferol and dietary calcium in HIV patients following antiretroviral therapy. Is it possible?

Objective: To evaluate whether treatment with 100,000 IU/month (equivalent to 3200 IU/day) of cholecalciferol and 1 g/day of dietary calcium supplementation in HIV patients following different cART regimens yields normal levels of vitamin D3 and PTH as well as whether changes in bone mineral density are clinically significant.Methods: Consecutive HIV patients following different cART regimens received 100,000 IU/month (equivalent to 3200 IU/day) of cholecalciferol and 1 g/day of dietary calcium supplementation. The participants underwent BMD assessment via dual energy X-ray absorptiometry of the spine and hip at baseline (T0) and after 24 months (T1). Levels of 25(OH) vitamin D3 and parathyroid hormone (PTH) were assessed at T0 and T1. Quantitative variables were assessed with a paired t-test, independent t-test or analysis of variance, as appropriate. A chi-squared analysis was used to assess the association between qualitative variables. A p-value <0.05 was considered significant. Patients were divided into three groups depending on the cART regimen.Results: A total of 79 patients were included (40 males, 51% and 39 females, 49%), with a mean age of 46.6 (SD ±11.2) years, a baseline CD4 count of 649 cells/µl and a mean 25 hydroxycholecalciferol (25(OH) D3) value of 25 + 10 ng/ml. After 24 months, the 25(OH) D3 increased to 40 + 11 ng/ml. The initial BMDs at T0 were estimated as 0.919 (±0.27) and 0.867 (±0.14) g/cm2 at the spine and hip, respectively. After 24 months, the BMD was 0.933 (±0.15) g/cm2 at the spine and 0.857 (±0.14) g/cm2 at the hip. Based on a BMD change exceeding 3%, a worsening was observed in 23% of patients at the spine and 27% at the hip, whereas stability or improvement was demonstrated in 77% of patients at the spine and 73% at the hip.Subgrouping patients based on antiretroviral therapy indicated that, at T1, there was a statistically significant increase in vitamin D3 concentration in all patients, while PTH concentration was not significantly reduced in patients taking tenofovir or efavirenz. BMD stability or improvement was demonstrated in 77% of patients at the spine and 73% at the hip after 24 months.The multivariate analysis confirms a decrease in vitamin D3 and an increase in PTH levels in smokers, as well higher vitamin D3 concentrations in males and lower spine BMDs in menopausal females.Conclusion: The proposed protocol of cholecalciferol and dietary calcium supplementation is safe and valid for correcting vitamin D abnormalities in almost all patients as well as reducing PTH levels in a high percentage of patients; however, it is not sufficient for normalization, particularly in patients exposed to tenofovir or efavirenz. At the spine, no significant BMD change was found in any of the therapy groups. At the hip, our data confirm a modest negative effect on bone mass caused by tenofovir and efavirenz.

Screening for Vitamin D Deficiency in Black Americans: Comparison of Total, Free, Bioavailable 25 Hydroxy Vitamin D Levels with Parathyroid Hormone Levels and Bone Mineral Density.

There is debate surrounding the adequacy of total and free 25 hydroxy vitamin D [25(OH)D] levels in black Americans who have inherently high bone mineral density [BMD] and low serum concentration of vitamin D binding proteins [VDBP]. Retrospective analysis of serum samples and BMD analyses from the African American Health Study [AAHS] cohort. The AAHS is a population-based longitudinal study initiated to examine issues of disability and frailty among urban-dwelling black Americans in the city of Saint Louis, Missouri. 122 men and 206 women, age 60.2 ± 4.3 years. Retrospective analysis. Total 25(OH)D, VDBP, PTH, and BMD of the lumbar spine and hip by dual energy x-ray photometry (DXA). Free and bioavailable vitamin D levels were calculated using serum concentrations and affinity constants for the VDBP (Gc1F and Gc1S) phenotypes. Serum total 25(OH)D levels were 14.6 ± 8.9 ng/mL (36 ± 22 nmol/L). Vitamin D insufficiency was estimated by compensatory elevations of PTH above the normal range (> 65 pg/mL). PTH levels were within the normal reference range in > 95% of the samples at total 25(OH)D levels ≥ 20 ng/mL (≥50 nmol/L). There was no difference in the correlation of the reciprocal relationship of vitamin D vs parathyroid hormone between the VDBP phenotypes. Receiver operating characteristic curve analyses indicated that serum total 25(OH)D discriminated sufficiency from insufficiency at least as well as the calculated levels of the free and bioavailable vitamin D. Very low levels of total 25(OH)D (≤ 8 ng/mL, ≤20 nmol/L) were associated with decreased BMD (p=0.02), but higher levels of 25(OH)D did not show statistical differences in BMD. Total 25(OH)D levels of ≤ 8ng/mL (≤20 nmol/L) are associated with clinically significant changes in BMD, whereas total 25(OH)D levels ≥ 20 ng/mL (≥50 nmol/L) suppressed PTH and were not associated with deficiencies in BMD. Lower levels of 25(OH)D may be acceptable for bone health in black than in white Americans.

Prediction of changes in bone mineral density in the elderly: contribution of "osteogenomic profile".

The rate of longitudinal bone loss (ΔBMD) is a risk factor for fracture. The variation in ΔBMD is partly determined by genetic factors. This study sought to define the association between an osteogenomic profile and ΔBMD. The osteogenomic profile was created from 62 BMD-associated SNPs from genome-wide association studies (GWAS) that were genotyped in 1384 elderly men and women aged 60+ years. Weighted genetic risk scores (GRS) were constructed for each individual by summing the products of the number of risk alleles and the sex-specific regression coefficients [associated with BMD from GWAS]. ΔBMD, expressed as annual percent change-in-BMD, was determined by linear regression analysis for each individual who had had at least two femoral neck BMD measurements. The mean ΔBMD was - 0.65% (SD 1.64%) for women and - 0.57% (SD 1.40%) for men, and this difference was not statistically significant (P = 0.32). In women, each unit increase in GRS was associated with 0.21% (SE 0.10) higher ΔBMD at the femoral neck (P = 0.036), and this association was independent of baseline BMD and age. In logistic regression analysis, each unit increase of GRS was associated with 41% odds (95%CI: 1.07-1.87) of rapid bone loss (ΔBMD ≤ - 1.2%/year; mean of rapid loss group = - 2.2%/year). There was no statistically significant association between ΔBMD and GRS in men. We conclude that the osteogenomic profile constructed from BMD-associated genetic variants is modestly associated with long-term changes in femoral neck BMD in women, but not in men.

Changes in bone mineral density after total parathyroidectomy without autotransplantation in the end-stage renal disease patients with secondary hyperparathyroidism

BackgroundThe patients with secondary hyperparathyroidism (SHPT) usually had reduced bone mineral density, which might lead to a substantial increase in osteoporosis, fracture and mortality. Although surgical intervention is effective in reducing parathyroid hormone (PTH) levels in suitable candidates refractory to medical therapy, the effect of surgery on bone mass changes still requires further evaluation. Thus, the aim of this study was to evaluate the characteristics of BMD changes after total parathyroidectomy (PTX) without autotransplantation and its associated factors.MethodsThe records of 34 patients who underwent successful total PTX without autotransplantation with a preoperative and postoperative dual energy X-ray absorptiometry (DEXA) scan in our institution within 4 years of operative intervention were reviewed. Correlation and regression analysis were used to identify factors that independently predict BMD changes.ResultsAt baseline, we found that the prevalence of osteoporosis seemed to be much higher in the load-bearing lumbar spine than in the hip, varying greatly even between different lumbar vertebrae. The bone loss in SHPT had its predilection site in the load-bearing cancellous bone. After curative total PTX without autotransplantation, BMD improved significantly in both lumbar spine and hip overall. The largest increase in BMD occurred at L4 vertebrae with the lowest pre-operative BMD. At the most affected site L4, BMD improved in up to 94.1% of patients: 86.2% had significant improvement, 5.9% moderate improvement, and 5.9% declining bone mineral density. Correlation and regression analysis suggested that percentage changes in BMD were predicted negatively by the preoperative BMD and positively by the preoperative parathyroid mass but not intact PTH levels.ConclusionTotal parathyroidectomy without autotransplantation could improve BMD of secondary hyperparathyroidism at L1-L4 and the hip. Furthermore, the large parathyroid glandular mass and the preoperative BMD predicted the BMD changes after surgery.

Pharmacological interventions for the prevention of insufficiency fractures and avascular necrosis associated with pelvic radiotherapy in adults.

Pelvic radiotherapy is a treatment delivered to an estimated 150,000 to 300,000 people annually across high-income countries. Fractures due to normal stresses on weakened bone due to radiotherapy are termed insufficiency fractures. Pelvic radiotherapy-related interruption of the blood supply to the hip is termed avascular necrosis and is another recognised complication. The reported incidences of insufficiency fractures are 2.7% to 89% and risk of developing avascular necrosis is 0.5%. These complications lead to significant morbidity in terms of pain, immobility and consequently risk of infections, pressure sores and mortality. To assess the effects of pharmacological interventions for preventing insufficiency fractures and avascular necrosis in adults over 18 years of age undergoing pelvic radiotherapy. We performed electronic literature searches in the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and DARE to 19 April 2017. We also searched trial registries. Further relevant studies were identified through handsearching of citation lists of included studies. Randomised controlled trials (RCTs) or non RCTs with concurrent comparison groups including quasi-RCTs, cluster RCTs, prospective cohort studies and case series of 30 or more participants were screened. We included studies assessing the effect of pharmacological interventions in adults over 18 years of age undergoing radical pelvic radiotherapy as part of anticancer treatment for a primary pelvic malignancy. We excluded studies involving radiotherapy for bone metastases. We assessed use of pharmacological interventions at any stage before or during pelvic radiotherapy. Interventions included calcium or vitamin D (or both) supplementation, bisphosphonates, selective oestrogen receptor modulators, hormone replacement therapy (oestrogen or testosterone), denosumab and calcitonin. Two review authors independently assessed trial quality and extracted data. We contacted study authors to obtain missing data. Data were to be pooled using the random-effects model if study comparisons were similar, otherwise results were to be reported narratively. We included two RCTs (1167 participants). The first RCT compared zoledronic acid with placebo in 96 men undergoing pelvic radiotherapy for non-metastatic prostate cancer.The second RCT had four treatment arms, two of which evaluated zoledronic acid plus adjuvant androgen suppression compared with androgen suppression only in 1071 men undergoing pelvic radiotherapy for non-metastatic prostate cancer.Both studies were at a moderate to high risk of bias and all evidence was judged to be of very low certainty.The studies provided no evidence on the primary outcomes of the review and provided limited data in relation to secondary outcomes, such that meta-analyses were not possible. Both studies focused on interventions to improve bone health in relation to androgen deprivation rather than radiation-related insufficiency fractures and avascular necrosis. Few fractures were described in each study and those described were not specific to insufficiency fractures secondary to radiotherapy. Both studies reported that zoledronic acid in addition to androgen deprivation and pelvic radiotherapy led to improvements in BMD; however, the changes in BMD were measured and reported differently. There was no available evidence regarding adverse effects. The evidence relating to interventions to prevent insufficiency fractures and avascular necrosis associated with pelvic radiotherapy in adults is of very low certainty. This review highlights the need for prospective clinical trials using interventions prior to and during radiotherapy to prevent radiation-related bone morbidity, insufficiency fractures and avascular necrosis. Future trials could involve prospective assessment of bone health including BMD and bone turnover markers prior to pelvic radiotherapy. The interventions for investigation could begin as radiotherapy commences and remain ongoing for 12 to 24 months. Bone turnover markers and BMD could be used as surrogate markers for bone health in addition to radiographic imaging to report on presence of insufficiency fractures and development of avascular necrosis. Clinical assessments and patient reported outcomes would help to identify any associated adverse effects of treatment and quality of life outcomes.