Prevent Bone Mineral Density Loss Research Articles

Preoperative prediction for periprosthetic bone loss and individual evaluation of bisphosphonate effect after total hip arthroplasty using artificial intelligence.

This study was designed to develop a model for predicting bone mineral density (BMD) loss of the femur after total hip arthroplasty (THA) using artificial intelligence (AI), and to identify factors that influence the prediction. Additionally, we virtually examined the efficacy of administration of bisphosphonate for cases with severe BMD loss based on the predictive model. The study included 538 joints that underwent primary THA. The patients were divided into groups using unsupervised time series clustering for five-year BMD loss of Gruen zone 7 postoperatively, and a machine-learning model to predict the BMD loss was developed. Additionally, the predictor for BMD loss was extracted using SHapley Additive exPlanations (SHAP). The patient-specific efficacy of bisphosphonate, which is the most important categorical predictor for BMD loss, was examined by calculating the change in predictive probability when hypothetically switching between the inclusion and exclusion of bisphosphonate. Time series clustering allowed us to divide the patients into two groups, and the predictive factors were identified including patient- and operation-related factors. The area under the receiver operating characteristic (ROC) curve (AUC) for the BMD loss prediction averaged 0.734. Virtual administration of bisphosphonate showed on average 14% efficacy in preventing BMD loss of zone 7. Additionally, stem types and preoperative triglyceride (TG), creatinine (Cr), estimated glomerular filtration rate (eGFR), and creatine kinase (CK) showed significant association with the estimated patient-specific efficacy of bisphosphonate. Periprosthetic BMD loss after THA is predictable based on patient- and operation-related factors, and optimal prescription of bisphosphonate based on the prediction may prevent BMD loss.

Zoledronate after denosumab discontinuation: Is repeated administrations more effective than single infusion?

After Denosumab (Dmab) discontinuation C-terminal telopeptide (CTX) levels increase, bone mineral density (BMD) decreases and multiple vertebral fractures (FX) may occur with relevant impact on women's health. A sequential therapy with bisphosphonates is recommended and the European Calcified Tissue Society (ECTS) proposed repeated zoledronate (ZOL) administrations in patients with persistently high CTX levels, although the efficacy of this schedule is unknown. In this retrospective study we describe BMD changes and FX rate in 52 patients managed according to the ECTS recommendations. We measured CTX levels and administered ZOL after one month from Dmab withdrawal (t0). After 6 months (t1), we administered a second ZOL infusion, if CTX levels were ≥280 ng/L. BMD changes and FX rate were assessed on average after 17 months from Dmab withdrawal. 75% of patients repeated ZOL infusion. In this group spine BMD declined significantly (-5.5 ± 5.6%), while it remained stable in the group with CTX levels <280 ng/L (-0.1 ± 5.5%, p = 0.008). All fractured patients (9.6%) had received >5 Dmab injections and two ZOL infusions. The BMD worsening after Dmab withdrawal was associated with CTX t1 (OR 2.9, IQR 1.3-6.6, p = 0.009) and spine BMD gain during Dmab therapy corrected for the number of Dmab injections (OR 3.0, IQR 1.2-7.2, p = 0.014). A CTX level at t1 > 212 ng/L had 100% sensitivity in predicting the BMD loss. In patients with uncontrolled CTX levels after Dmab withdrawal, two ZOL infusions at 6 months apart do not prevent BMD loss and FX.

Antidiabetic drug administration prevents bone mineral density loss: Evidence from a two-sample Mendelian randomization study.

The aim of this study was to investigate the effect of common antidiabetic drugs on BMD by two-sample Mendelian randomization (MR). The single nucleotide polymorphisms that were strongly associated with insulin, metformin, rosiglitazone and gliclazide were extracted as instrumental variables (IVs) for MR analysis. The inverse variance weighted (IVW) method was used as the primary MR method to assess the causal effect of antidiabetic drugs on BMD, and other MR methods, including Weighted median, MR Egger and Weighted mode, were used for complementary analysis. Reliability and stability were assessed by the leave-one-out test. In the present work, IVW estimation of the causal effect of insulin on heel BMD demonstrated that there was a null effect of insulin on heel BMD (β = 0.765; se = 0.971; P = 0.430), while metformin treatment had a positive effect on heel BMD (β = 1.414; se = 0.460; P = 2.118*10-3). The causal relationship between rosiglitazone and heel BMD analysed by IVW suggested that there was a null effect of rosiglitazone on heel BMD (β = -0.526; se = 1.744; P = 0.763), but the causal effect of gliclazide on heel BMD evaluated by IVW demonstrated that there was a positive effect of gliclazide on heel BMD (β = 2.671; se = 1.340; P = 0.046). In summary, the present work showed that metformin and gliclazide have a role in reducing BMD loss in patients with diabetes and are recommended for BMD loss prevention in diabetes.

Prune Consumption Attenuates Proinflammatory Cytokine Secretion and Alters Monocyte Activation in Postmenopausal Women: Secondary Outcome Analysis of a 12-Mo Randomized Controlled Trial: The Prune Study

BackgroundProinflammatory cytokines are implicated in the pathophysiology of postmenopausal bone loss. Clinical studies demonstrate that prunes prevent bone mineral density loss; however, the mechanism underlying this effect is unknown. ObjectiveWe investigated the effect of prune supplementation on immune, inflammatory, and oxidative stress markers. MethodsA secondary analysis was conducted in the Prune Study, a single-center, parallel-arm, 12-mo randomized controlled trial of postmenopausal women (55–75 y old; n = 235 recruited; n = 183 completed) who were assigned to 1 of 3 groups: “no-prune” control, 50 g prune/d and 100 g prune/d groups. At baseline and after 12 mo of intervention, blood samples were collected to measure serum high-sensitivity C-reactive protein (hs-CRP), serum total antioxidant capacity (TAC), plasma 8-isoprostane, proinflammatory cytokines [interleukin (IL)-1β, IL-6, IL-8, monocyte chemoattractant protein-1, and tumor necrosis factor (TNF)-α] concentrations in plasma and lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs) culture supernatants, and the percentage and activation of circulating monocytes, as secondary outcomes. ResultsPrune supplementation did not alter hs-CRP, TAC, 8-isoprostane, and plasma cytokine concentrations. However, percent change from baseline in circulating activated monocytes was lower in the 100 g prune/d group compared with the control group (mean ± SD, −1.8% ± 4.0% in 100 g prune/d compared with 0.1% ± 2.9% in control; P < 0.01). Furthermore, in LPS-stimulated PBMC supernatants, the percent change from baseline in TNF-α secretion was lower in the 50 g prune/d group compared with the control group (−4.4% ± 43.0% in 50 g prune/d compared with 24.3% ± 70.7% in control; P < 0.01), and the percent change from baseline in IL-1β, IL-6, and IL-8 secretion was lower in the 100 g prune/d group compared with the control group (−8.9% ± 61.6%, −4.3% ± 75.3%, −14.3% ± 60.8% in 100 g prune/d compared with 46.9% ± 107.4%, 16.9% ± 70.6%, 39.8% ± 90.8% in control for IL-1β, IL-6, and IL-8, respectively; all P < 0.05). ConclusionsDietary supplementation with 50–100 g prunes for 12 mo reduced proinflammatory cytokine secretion from PBMCs and suppressed the circulating levels of activated monocytes in postmenopausal women.This trial was registered at clinicaltrials.gov as NCT02822378.

Potential alleviation of bone mineral density loss with Janus kinase inhibitors in rheumatoid arthritis.

Rheumatoid arthritis (RA) is characterized by localized bone loss, general osteoporosis and increased fracture risks. Tumour necrosis factor inhibitors (TNFi), non-tumour necrosis factor inhibitors (non-TNFi) biologic, Janus kinase inhibitors (JAKi) had shown the suppression effects to osteoclast activation and improvement of bone mineral density (BMD). Anti-cyclic citrullinated peptide antibody (ACPA) is associated with osteoclast activation and the resultant bone loss. However, few studies have compared BMD changes among patients with RA treated with targeted therapies that have different mechanisms of action. This retrospective study recruited patients with RA who had undergone BMD testing twice. Changes in the BMD were compared using the generalized estimating equation (GEE) in treatment groups that received conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), TNFi, non-TNFi biologics, and JAKi. In total, 362 patients with RA were enrolled (csDMARDs, n = 153, TNFi, n = 71, non-TNFi biologics, n = 108, JAKi, n = 30). We observed greater changes in femoral BMD (left, 0.06, 95% CI 0.01-0.12, p = 0.016; right, 0.09, 95% CI 0.04-0.15, p = 0.001 by GEE) following JAKi treatment as compared with other treatments. Compared to the ACPA-negative group, patients with ACPA positivity exhibited greater improvement in the femoral BMD (left, 0.09, 95% CI 0.02-0.15, p = 0.008; right, 0.11, 95% CI 0.05-0.18, p = 0.001). Compared to other targeted therapies, JAKi might exert a more potent effect to prevent BMD loss, specifically in ACPA-positive patients with RA, and could be a potential therapeutic option to mitigate generalized bone loss. Key Points •JAKi therapy inhibits systemic bone loss in patients with RA. •ACPA-positive RA patients exhibited a greater BMD improvement than ACPA-negative RA patients. •JAKi might more potently prevent BMD decline than conventional synthetic or biological DMARDs.

The Impact of Seropositivity on Systemic Bone Loss in Rheumatoid Arthritis-A 3-Year Interim Analysis of a Longitudinal Observational Cohort Study.

ObjectiveTo explore the impact of seropositivity on systemic bone loss in rheumatoid arthritis (RA).MethodsWe conducted an interim analysis of the RA registry. Patients were examined with dual-energy X-ray absorptiometry at baseline and again 3 years later. Participants were grouped into seropositive (SPRA) and seronegative (SNRA) based on the presence or absence of rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide antibodies (ACPA). After matching (1:2) for age and sex, SNRA and SPRA patients were divided into groups A and B. Each matched group (A or B) was further subdivided according to the number of antibodies present (0, group I; 1, group II; 2, group III). Multiple ordinary least squares regression was used with the dependent variables to develop a model to predict bone mineral density (BMD) change.ResultsA total of 477 participants who completed a 3-year observation period were included. After matching, 312 participants were enrolled (group A, 104; group B, 208). Three years later, group B had significant BMD reduction in the femoral neck (FN) (p < 0.001), total hip (TH) (p = 0.001), and first through fourth lumbar vertebrae (L1–4) (p = 0.006), while group A had bone loss only at FN (p = 0.002). Groups I, II, and III included 104, 52, and 156 participants, respectively. Compared to baseline, BMD decreased significantly at FN (p = 0.002) in group I, FN (p < 0.001) in group II, and FN (p < 0.001), TH (p = 0.002), and L1–4 (p = 0.016) in group III. In terms of regression-adjusted percent change in BMD, more significantly negative changes were found at all measured sites in group B (p < 0.001, all) and at TH and L1–4 within groups I-III (p for trend < 0.001 and < 0.001, respectively). Regardless of antibodies, anti-osteoporotic therapy can preserve bone density in RA patients.ConclusionAfter 3 years, SPRA patients lost more bone density than SNRA patients. More attention should be paid to SPRA patients, especially those with double-positive antibodies, including a vigorous evaluation of BMD and fracture risk. Anti-osteoporotic therapy can prevent BMD loss irrespective of autoantibodies.

Nutrition, Physical Activity, and Dietary Supplementation to Prevent Bone Mineral Density Loss: A Food Pyramid.

Bone is a nutritionally modulated tissue. Given this background, aim of this review is to evaluate the latest data regarding ideal dietary approach in order to reduce bone mineral density loss and to construct a food pyramid that allows osteopenia/osteoporosis patients to easily figure out what to eat. The pyramid shows that carbohydrates should be consumed every day (3 portions of whole grains), together with fruits and vegetables (5 portions; orange-colored fruits and vegetables and green leafy vegetables are to be preferred), light yogurt (125 mL), skim milk (200 mL,) extra virgin olive oil (almost 20 mg/day), and calcium water (almost 1 l/day); weekly portions should include fish (4 portions), white meat (3 portions), legumes (2 portions), eggs (2 portions), cheeses (2 portions), and red or processed meats (once/week). At the top of the pyramid, there are two pennants: one green means that osteopenia/osteoporosis subjects need some personalized supplementation (if daily requirements cannot be satisfied through diet, calcium, vitamin D, boron, omega 3, and isoflavones supplementation could be an effective strategy with a great benefit/cost ratio), and one red means that there are some foods that are banned (salt, sugar, inorganic phosphate additives). Finally, three to four times per week of 30–40 min of aerobic and resistance exercises must be performed.

Local and generalized bone loss in rheumatoid arthritis

The article presents a review of cross-sectional studies and long-term prospective observations dedicated to changes in bone mineral density (BMD) in patients with rheumatoid arthritis (RA) and factors influencing it. The relationship between local bone loss (erosion count) and generalized BMD loss was noted. It is indicated that existing RA treatment strategies are aimed at suppressing inflammation rather than preventing bone resorption. There is evidence that anti-inflammatory therapy using glucocorticoids, methotrexate, and biologic DMARDs in combination with antiresorptive drugs (bisphosphonates and denosumab) helps prevent BMD loss and the progression of erosions. It is emphasized that osteoporosis in RA, which belongs to the immune-mediated secondary osteopathies, is one of the most frequent and serious complications of RA, which determine the unfavorable course and prognosis of the underlying disease.

Impact of bone-active drugs and underlying disease on bone health after lung transplantation: A longitudinal study

Introductionthe effect of bone-active drugs on the risk of fragility fractures (Fx), bone mineral density (BMD) and trabecular bone score (TBS) changes in patients receiving lung transplantation (LTx) is largely unknown. This study assessed the bone-active drugs effect in patients undergoing LTx both with (CF) and without (nCF) cystic-fibrosis. MethodsWe evaluated incident Fx, both clinical and morphometric vertebral Fx by spinal X-ray, BMD and trabecular bone score (TBS) in 117 patients (CF=50, nCF n = 67) before and 24-months after LTx. A bone-active therapy was proposed to all LTx candidates. Results83.8% of patients started a bone-active drug. Lumbar-spine (LS) T-score improved significantly only in treated patients (-1.4 ± 1.0 vs -2.0±1.0, p = 0.0001), whereas femur BMD and TBS remained stable in treated and not treated subjects. The rate of incident Fx was 15.3%, with no difference between treated and not treated patients. After LTx, LS T-score improved significantly only in nCF group (-1.3 ± 1.0 vs -1.8 ± 1.1, p = 0.0001), while femur remained stable in both nCF and CF groups. Patients with CF showed a significant Z-TBS increase (-3.6 ± 1.7 vs -3.0 ± 1.7, p = 0.019) and a lower Fx incidence as compared with nCF patients (4.1% vs 24.2%, p =0.003). Incident Fx were associated with nCF diagnosis (OR 7.300, CI95% 1.385–38.461, p = 0.019) regardless of prevalent Fx, previous glucocorticoid therapy and bone-active therapy introduced at least 6 months before LTx. ConclusionsA prompt medical intervention helps in preventing BMD loss after LTx. As compared with nCF patients, CF patients show a TBS increase and a lower Fx risk after LTx.

English

Objective: The association between sex hormones and bone mineral density (BMD) has been studied in sedentary women, whereas only few studies have evaluated trained females. Therefore, the aim of this study was to assess the influence of sex hormones on BMD in well-trained females with different hormonal profiles: eumenorrheic females, oral contraceptive (OC) users and postmenopausal women. The secondary purpose was to determine if maximal oxygen consumption (V̇ O2max) or maximal back squat strength (1RM) could be good predictors of BMD in this population. Methods: Sixty-eight eumenorrheic, forty-one monophasic-OC users and sixteen postmenopausal well-trained females participated in this study. A Dual-energy X-ray Absorptiometry scan (DXA), a basal blood sample and a maximal back squat and/or a maximal treadmill test were performed. In order to measure all volunteers under similar hormonal conditions (low sex hormone levels), all tests were carried out during the early follicular phase for the eumenorrheic females and in the withdrawal phase for the OC group. Results: One way ANCOVA reported lower values of BMD in postmenopausal (1.13±0.07g/cm2) than in eumenorrheic (1.19±0.08 g/cm2) (p=0.003) and OC users (1.17±0.07 g/cm2) (p=0.030). Pearson´s correlation showed a positive relationship between BMD and 1RM (p&lt;0.001), but not with V̇ O2max. Conclusions: Lower BMD has been reported in postmenopausal women compared to both, eumenorrheic females and OC users. BMD loss after menopause seems to be not fully compensated by exercise, but this could effectively mitigate it. Moreover, 1RM back squat reported a slight association to BMD. Hence, strength training may be the best choice to prevent BMD loss.

Scopolin Attenuates Osteoporotic Bone Loss in Ovariectomized Mice.

Bone remodeling is a renewal process regulated by bone synthesis (osteoblasts) and bone destruction (osteoclasts). A previous study demonstrated that Lycii radicis cortex (LRC) extract inhibited ovariectomized (OVX)-induced bone loss in mice. This study investigated the anti-osteoporotic effects of bioactive constituent(s) from the LRC extract. The effective compound(s) were screened, and a single compound, scopolin, which acts as a phytoalexin, was chosen as a candidate component. Scopolin treatment enhanced alkaline phosphatase activity and increased mineralized nodule formation in MC3T3-E1 pre-osteoblastic cells. However, osteoclast differentiation in primary-cultured monocytes was reduced by treatment with scopolin. Consistently, scopolin treatment increased osteoblast differentiation in the co-culture of monocytes (osteoclasts) and MC3T3-E1 (osteoblast) cells. Scopolin treatment prevented bone mineral density loss in OVX-induced osteoporotic mice. These results suggest that scopolin could be a therapeutic bioactive constituent for the treatment and prevention of osteoporosis.

Fracture risk and management of discontinuation of denosumab therapy: a systematic review and position statement by ECTS.

Denosumab discontinuation is characterized by an increase in bone turnover overriding pre-treatment status, a rapid bone loss in the majority and multiple vertebral fractures (VFx) in some patients. A working group of the European Calcified Tissue Society (ECTS) performed an updated systematic review of existing literature on changes of bone turnover, bone mineral density (BMD), and fracture risk after denosumab discontinuation and provided advice on management based on expert opinion. Important risk factors for multiple VFx following denosumab cessation are prevalent VFx, longer duration off therapy, greater gain in hip BMD during therapy, and greater loss of hip BMD after therapy according to a retrospective analysis of the FREEDOM Extension Study. Case series indicate that prior bisphosphonate therapy mitigates the biochemical rebound phenomenon after denosumab discontinuation, but it is uncertain whether this attenuation prevents BMD loss and fractures. Current evidence indicates partial efficacy of subsequent antiresorptive treatment with results seemingly dependent on duration of denosumab treatment. A careful assessment of indications to start denosumab treatment is advised, especially for younger patients. A case for long-term treatment with denosumab can be made for patients at high fracture risk already on denosumab treatment given the favorable efficacy and safety profile. In case of denosumab discontinuation, alternative antiresorptive treatment should be initiated 6 months after the final denosumab injection. Assessment of bone turnover markers may help define the optimal regimen, pending results of ongoing RCTs. Patients having sustained VFx should be offered prompt treatment to reduce high bone turnover.

The Utility of Prophylactic Zoledronic Acid in Patients Undergoing Lung Transplantation

Osteoporosis is prevalent among lung transplant candidates and is exacerbated post-transplant by immunosuppressive therapy. Low bone mineral density (BMD) is a well-recognized surrogate for fragility fracture risk, which is associated with significant morbidity and mortality. Intravenous zoledronic acid (ZA) effectively reduces BMD loss and prevents fractures in postmenopausal osteoporosis. Many groups, ours included, prophylactically treat lung transplant recipients (LTR) with bisphosphonates, but no documented consensus currently exists. Our protocol comprises ZA every 6-months from transplant wait-listing, with interval reassessment to guide ongoing treatment. We evaluate the impact of a dose of ZA within 6 months of transplantation on BMD and fracture occurrence. A retrospective analysis was performed on all adult LTR from April 2012 to October 2014, of which 60 met our inclusion criteria. LTR who received ZA within 6 months of transplantation (n = 37) were compared to those who did not (n = 23), and followed up for a minimum of three years. Outcome measures were BMD change at the lumbar spine and femur (primary), and fracture occurrence (secondary). LTR treated with ZA within 6 months of transplantation experienced a median BMD change of +8.11% at the lumbar spine and +1.39% at the femur, compared to −1.20% and −3.92%, respectively, in LTR who did not receive a ZA dose within 6 months of transplantation (p = 0.002 & p = 0.008 respectively). Our findings indicate that prophylactic ZA within 6 months of transplantation prevents BMD loss in LTR.

Anti-Osteoporotic Effects of the Herbal Mixture of Cornus officinalis and Achyranthes japonica In Vitro and In Vivo.

Osteoporosis is a porous bone disease caused by bone density loss, which increases the risk of fractures. Cornus officinalis (CO) and Achyranthes japonica (AJ) have been used as traditional herbal medicine for various disorders in East Asia. Although the anti-osteoporotic effects of single extract of CO and AJ have already been reported, the synergistic effect of a combined mixture has not been studied. In this study, we investigated the effects of a CO and AJ herbal mixture on osteoporosis in in vitro and in vivo models. The results demonstrate that treatment with the CO and AJ mixture significantly promoted osteoblast differentiation of MC3T3-E1 mouse preosteoblasts through the upregulation of osteoblastic differentiation-associated genes such as alkaline phosphatase (Alpl), runt-related transcription factor 2 (Runx2), and bone gamma-carboxyglutamic acid-containing protein (Bglap), while the mixture significantly inhibited differentiation of osteoclasts isolated from primary-cultured mouse monocytes. In addition, oral administration of CO and AJ mixture significantly prevented bone mineral density loss and trabecular bone structures in an ovariectomy-induced osteoporotic mouse model. These results suggest that the combination treatment of CO and AJ mixture might be a beneficial therapy for osteoporosis.

Influence of Hydroxyapatite Coating for the Prevention of Bone Mineral Density Loss and Bone Metabolism after Total Hip Arthroplasty: Assessment Using 18F-Fluoride Positron Emission Tomography and Dual-Energy X-Ray Absorptiometry by Randomized Controlled Trial.

Background Hydroxyapatite- (HA-) coated implants tend to achieve good osteoinductivity and stable clinical results; however, the influence of the coating on the prevention of bone mineral density (BMD) loss around the implant is unclear. The purpose of this randomized controlled trial was to evaluate the effectiveness of HA-coated implants for preventing BMD loss and to determine the status of bone remodeling after total hip arthroplasty (THA), making comparisons with non-HA-coated implants. Methods A total of 52 patients who underwent primary THA were randomly allocated to HA and non-HA groups. BMD was measured by dual-energy X-ray absorptiometry (DEXA) at 1 week postoperation to form a baseline measurement, and then 24 weeks and 48 weeks after surgery. The relative change in BMD was evaluated for regions of interest (ROIs) based on the Gruen zone classifications. 18F-fluoride positron emission tomography (PET) was performed at 24 weeks postsurgery, and the maximum standardized uptake values (SUVmax) were evaluated in the proximal (HA-coated) and distal (non-HA-coated) areas in both groups. Results There were significant differences in BMD loss in ROIs 3 and 6 (p = 0.03), while no significant difference was observed in ROI 7 at either 24 or 48 weeks postsurgery. There was no significant correlation between PET uptake and BMD (24 or 48 weeks) in either group. Conclusion The influence of a HA coating in terms of BMD preservation is limited. No significant correlation was found between BMD and SUVmax measured by PET, either with or without the use of a HA coating.

Effect of switching administration of alendronate after teriparatide for the prevention of BMD loss around the implant after total hip arthroplasty, 2-year follow-up: a randomized controlled trial

BackgroundStress shielding after total hip arthroplasty (THA) can induce bone mineral density (BMD) loss around the femoral implant. Several studies using drug have described methods to prevent BMD loss around implants following THA. Switching from teriparatide to alendronate was reported to increase lumbar BMD; on the other hands, it is unclear whether switching from teriparatide to alendronate is effective around the implant. The aim of this study is that changes in BMD is compared in patients switched from teriparatide to alendronate, in patients treated with alendronate alone, and in control patients without medication after total hip arthroplasty.Patients and methodsPatients were randomized into three groups, those switched to alendronate after teriparatide (switch: n = 17), those receiving continuous alendronate (ALD: n = 15), and control untreated patients (control: n = 16) and followed up for 2 years after THA. Baseline periprosthetic BMD was measured by dual-energy X-ray absorptiometry (DEXA) 1 week after THA, followed by subsequent measurements at 1 and 2 years postoperatively. Lumbar BMD was also evaluated at preoperatively, 1 and 2 years postoperatively.ResultsTwo years after surgery, BMD (%) at zone 1 was significantly higher in the switch group than in the control group (P = 0.02). BMD (%) at zone 7 was significantly higher in the switch and ALD groups than in the control group (P = 0.01, P = 0.03). Lumbar BMD (%) anterior-posterior (AP) side was significantly higher in the switch group than in the ALD and control groups 2 years after surgery. On the other hand, lumbar BMD (%) lateral side was significantly higher in the switch and ALD groups than control group 2 years after surgery.ConclusionsSwitching therapy had a significant effect on BMD of the lumbar spine and zones 1 and 7 at 2 years postoperatively. At zone 1 in particular, it was found to be more effective than ALD alone.Trial registrationUMIN, registry number UMIN000016158. Registered 8 January 2015

The effects of adjuvant endocrine therapy on bone health in women with breast cancer.

In women with oestrogen receptor (ER)-positive early breast cancer, oestradiol is important for breast cancer development and progression. Endocrine therapy prevents the deleterious effects of oestradiol in breast tissue by systemically depleting oestradiol concentration (aromatase inhibitors) or preventing its local action in breast tissue (selective oestrogen receptor modulators i.e. tamoxifen), thereby improving oncological outcomes. Use of aromatase inhibitors in postmenopausal women and ovarian function suppression with either tamoxifen or aromatase inhibition in premenopausal women, consequent to systemic oestradiol depletion, exerts detrimental effects on skeletal health. The oestradiol-deficient state causes increased bone remodelling and a negative bone balance. This results in bone loss, microstructural deterioration and bone fragility predisposing to fractures. Similar effects are also seen with tamoxifen in premenopausal women. In contrast, use of tamoxifen in postmenopausal women appears to exert protective effects on bone but studies on fracture risk are inconclusive. The longevity of women with ER-positive breast cancer treated with adjuvant endocrine therapy emphasises the need to mitigate the adverse skeletal effects of these therapies in order to maximise benefit. In general, fractures are associated with increased morbidity, mortality and are a high socioeconomic burden. Whilst the efficacy of antiresorptive therapy in preventing bone mineral density loss in postmenopausal women has been established, further clinical trial evidence is required to provide guidance regarding fracture risk reduction, when to initiate and stop treatment, choice of agent and optimal management of bone health in premenopausal women receiving endocrine therapy. In addition, potential oncological benefits of antiresorptive therapies will also need to be considered.

Russian federal clinical guidelines on the diagnostics, treatment, and prevention of osteoporosis

Screening using the Fracture Risk Assessment Tool (FRAX) is recommended in all postmenopausal woman and mеn over 50 (A1) in order to identify individuals with high probability of fractures. It is recommended to diagnose osteoporosis and start treatment in patients with fragility fracture of large bones of the skeleton and/or high individual probability of major fragility fractures (FRAX) and/or detected decrease in bone mineral density (BMD) up to –2.5 T-score as assessed by DXA in the femoral neck and/or lumbar vertebrae (A1). Patients with back pain, lifetime height loss of 4 cm or height loss of 2 cm since a previous medical examination, those who receive glucocorticoids, patients with long lasting decompensated type 2 diabetes mellitus, or those receiving insulin therapy, as well as patients who were previously diagnosed with fragility fractures at the other sites are advised to underwent standard lateral X-ray imaging of the spine (Th4—L5) in order to verify the presence of compression vertebral fractures (B1).&#x0D; Dual-energy X-ray absorptiometry (DXA) is recommended for individuals whose 10-year probability of major osteoporotic fracture (FRAX) falls within the medium risk group (B1). It is recommended to include the trabecular bone score (TBS) the FRAX algorithm in order to improve the sensitivity of this method (B1).&#x0D; Laboratory testing is recommended for the differential diagnosis with other causes of increased skeletal fragility in all patients with newly diagnosed osteoporosis and when previously prescribed antiosteoporostic treatment was ineffective (B1).&#x0D; Bisphosphonates (BPs), antibodies to receptor activator of nuclear factor kappa-beta ligand (RANKL) (denosumab), or parathyroid hormone analogue (teriparatide) are equally recommended to prevent fragility fractures and increase BMD in patients with osteoporosis (A1). Denosumab is also recommended to prevent BMD loss and fractures in females receiving aromatase inhibitors therapy for breast cancer and males with prostate cancer receiving hormone-deprivation therapy and having no bone metastases (A1). Since teriparatide has the anabolic effect, it is recommended as the first line treatment in patients with severe osteoporosis having history of vertebral fractures, in the individuals with very high risk of fragility fractures, or in the cases when antiresorptive treatment was ineffective (B1). All medications for treatment of osteoporosis are recommended in combination with calcium and vitamin D supplements (A1).

Reconstruction method as an independent risk factor for postoperative bone mineral density loss in gastric cancer.

No study has compared the incidence of postoperative bone metabolic disorders between Billroth-I (B-I) and Roux-en-Y (R-Y) reconstructions after distal gastrectomy (DG) for gastric cancer (GC). In this study, we wished to examine the impact of reconstruction method on postoperative bone mineral density (BMD) loss. We investigated a total of 148 consecutive patients who underwent DG with B-I or R-Y reconstruction for stage I GC between 2008 and 2012. We retrospectively assessed the BMD data using computed tomography attenuation values of the first lumbar vertebra after surgery. In multivariate analysis for the whole study series, R-Y reconstruction was identified as an independent risk factor for BMD loss after DG (P<0.0001; OR=5.60; 95% CI=2.38-13.98). Propensity score match analysis was used to overcome bias because of the different covariates for the two groups; even though the 37 patients in the B-I group and the 37 patients in the R-Y group had no significant difference among characteristics, B-I reconstruction was validated to have superiority over R-Y reconstruction for preventing BMD loss in the first 3years after DG. The cumulative hazard ratio of osteoporosis after gastrectomy was significantly higher in the R-Y group than in the B-I group (P=0.0427). Billroth-I reconstruction might be a preferable method for preventing BMD loss after gastrectomy in GC patients.

Combining Amino Acid and Vitamin D Supplementation with Exercise Training Increases Skeletal Muscle Mass and Prevent Bone Mineral Density Loss in Participants with Low Muscle Mass

This study evaluated the impact of exercise training with amino acid and vitamin D supplementation on muscle and bone mass in participants with low muscle volume. Twenty-nine Japanese participants (56-84 years old) were enrolled and assigned into the supplement (n=15) and non-supplement (n=14) groups. All participants underwent a 6-month exercise program. Supplements and nutrition support were provided to the participants in the supplement group for 12 weeks. Body composition and whole bone mineral density (BMD) were measured using dual energy x-ray absorptiometry. The outcomes, including body composition, whole BMD, and skeletal muscle mass index (SMI), were evaluated twice: pre- and post-intervention. The SMI was 6.51(6.28; 7.14) and 5.58 (5.24; 6.05) (kg/m2) in men and women, respectively. The average SMI change was 0.13% (-0.05%; 0.31%) and 2.33% (-0.88%; 5.48%); [mean (lower; upper quartile)]. The average BMD loss in the non-supplement group was -2.78%, and the BMD increased in the supplement group by 4.34%; there was an absolute difference between the two groups (p&lt;0.05). After the intervention, serum myostatin was changed (p=0.001, non-supplement&gt;supplement), serum vitamin D was increased (p=0.03; supplement&gt;non-supplement), and BMD was maintained (p=0.03, supplement&gt;non-supplement). There was a significant difference in the serum myostatin level at baseline and at 6-month in the non-supplement group, with a mean difference of 483.78 ng/ml (p=0.01). There was no significant improvement in the total lean mass, and handgrip strength. Resistance exercise combined with an amino acid supplement affects muscle and bone mass in the short-term intervention.