Glucagon-like Peptide-1 Receptor Agonists and Diabetic Osteopathy: Another Positive Effect of Incretines? A 12 Months Longitudinal Study.

Diabetic osteopathy is a frequent complication in patients with type 2 diabetes mellitus (T2DM). The association between T2DM and increased fracture risk has led to study the impact of new antidiabetic drugs on bone metabolism. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are incretin mimetic drugs which have many pleiotropic properties. The relationship between GLP-1RAs and bone is very complex: while in vitro and animal studies have demonstrated a protective effect on bone, human studies are scarce. We led a 12 months longitudinal study evaluating bone changes in 65 patients withT2DM for whom a therapy with GLP-1RAs had been planned. Fifty-four T2DM patients completed the 12-month study period; of them, 30 had been treated with weekly dulaglutide and 24 with weekly semaglutide. One-year therapy with GLP-1RAs resulted in a significant reduction in weight and BMI. Bone mineral density (BMD), bone metabolism, trabecular bone score (TBS), adiponectin, and myostatin were evaluated before and after 12 months of GLP-1RAs therapy. After 12 months of therapy bone turnover markers and adiponectin showed a significant increase, while myostatin values showed a modest but significant reduction. BMD-LS by DXA presented a significant reduction while the reduction in BMD-LS by REMS was not significant and TBS values showed a marginal increase. Both DXA and REMS techniques showed a modest but significant reduction in femoral BMD. In conclusion, the use of GLP-1RAs for 12 months preserves bone quality and reactivates bone turnover. Further studies are needed to confirm whether GLP-1RAs could represent a useful therapeutic option for patients with T2DM and osteoporosis.

Neglecting Bone Health: A Critical Gap in Management of Muscle Spasticity with Botulinum Toxin in Spinal Cord Injury.

Neuromuscular inhibitors have been quickly advanced from being used only for aesthetic purposes to being used as a treatment for musculoskeletal pain and muscle spasticity. This phenomenon stems from the diminished force exerted by muscles, which are essential for bone remodeling. In this context, it is hypothesized that botulinum toxin (BTX) might exert a direct influence on bone resorption. Although such treatments have the potential to provide patients with significant relief, bone loss occurring due to elective muscle paralysis has yet to be examined in clinical trials. The disuse model resulting from spinal cord injury, characterized by the absence of ground reaction and muscle forces, provides an ideal context for exploring the skeletal ramifications of intramuscular BTX injection. This approach enables an investigation into the intricate interplay between muscle and bone, encompassing the impact of spasticity on bone preservation, the potential positive and negative outcomes of BTX on bone metabolism, and the involvement of the autonomic nervous system in bone remodeling regulation. This paper presents a narrative review of research findings on the disturbance of the typical balance between muscles and bones caused by acute muscle paralysis from BTX, resulting in osteopenia and bone resorption.

Bisphosphonate treatment for skeletal complications in paediatric cancer-Experience from a single tertiary centre.

AIMS: The aim was to analyse the use and safety of bisphosphonate treatment for metabolic bone complications in paediatric cancer patients. METHODS: We retrospectively describe our experience with bisphosphonate treatment in 25 childhood cancer patients (aged <18 years) in a single tertiary hospital between 1999 and 2020. RESULTS: The most common primary diagnosis was acute lymphoblastic leukaemia (n = 16) and Hodgkin lymphoma (n = 3). Eleven patients (44%) had received allogeneic stem cell transplantation and two patients autologous stem cell transplantation. Sixteen patients (64%) had been treated with radiotherapy, either total-body (n = 11) or local (n = 5). The main indication for bisphosphonates was osteoporosis with vertebral compression fractures in 13/25, osteonecrosis in 6/25 and hypercalcaemia in 2/25. The bisphosphonate treatment was started on average 13 (range 0-76) months after the diagnosis of the bone complication. Bisphosphonate treatment lasted between weeks (hypercalcaemia) to 5 years (severe osteoporosis). Mild, non-symptomatic hypophosphatemia (n = 8), hypocalcaemia (n = 6) and moderate, transient pain (n = 6) were the most common adverse effects. No severe side effects were observed even when bisphosphonates were administered concomitantly with chemotherapy. Bone mineral density significantly improved with the bisphosphonate treatment (mean lumbar spine Z-score -1.17 vs. -0.07, p < 0.001). CONCLUSION: Bisphosphonate treatment was well tolerated in this paediatric patient cohort.

Pro-Osteogenic Effect of the Nutraceutical BlastiMin Complex® in Women with Osteoporosis or Osteopenia: An Open Intervention Clinical Trial.

Osteoporosis is a chronic disease that affects millions of patients worldwide and is characterized by low bone mineral density (BMD) and increased risk of fractures. Notably, natural molecules can increase BMD and exert pro-osteogenic effects. Noteworthily, the nutraceutical BlastiMin Complex® (Mivell, Italy, European Patent Application EP4205733A1) can induce differentiation of human bone marrow mesenchymal stem cells (BM-MSCs) in osteoblasts and can exert in vitro pro-osteogenic and anti-inflammatory effects. Thus, the purpose of this study was to verify the effects of BlastiMin Complex® on bone turnover markers (BTMs) and BMD in patients with senile and postmenopausal osteopenia or osteoporosis. The efficacy of BlastiMin Complex® on BTMs in serum was evaluated through biochemical assays. BMD values were analyzed by dual-energy X-ray absorptiometry (DXA) and Radiofrequency Echographic Multi Spectrometry (R.E.M.S.) techniques, and the SNPs with a role in osteoporosis development were evaluated by PCR. Clinical data obtained after 12 months of treatment showed an increase in bone turnover index, a decrease in C-reactive protein levels, and a remarkable increase in P1NP levels, indicating the induction of osteoblast proliferation and activity in the cohort of 100% female patients recruited for the study. These findings show that the nutraceutical BlastiMin Complex® could be used as an adjuvant in combination with synthetic drugs for the treatment of osteoporosis pathology.

[Metabolic bone diseases : what's new in 2023]. / Maladies osseuses : ce qui a changé en 2023.

The sequential effects of romosozumab and denosumab in osteoporosis are shown in real-life, while the mechanisms of post-denosumab rebound are reviewed extensively. A network meta-analysis confirms the superiority of anabolics vs anti-resorptives on fracture reduction, while the latter shown a reduction of mortality in a large population-based study. Fracture risk prediction by FRAXPlus is improved. New meta-analyses confirm the benefits of Vitamin D on fractures and falls. Finally, multiples trials with new molecules for the treatment of rare bone diseases, including osteogenesis imperfecta, fibrous dysplasia and hypoparathyroidism, shown promising results.

Dans l'ostéoporose, les effets séquentiels du romosozumab et du dénosumab se précisent et les mécanismes du rebond à l'arrêt de ce dernier font l'objet d'une revue détaillée. Une méta-analyse en réseau confirme la supériorité des traitements anaboliques sur les antirésorbtifs, alors que l'effet de ces derniers sur la réduction de la mortalité est démontré dans une large étude populationnelle. La prédiction du risque fracturaire est améliorée par l'outil FRAXPlus. De nouvelles méta-analyses des bénéfices de la vitamine D sur le risque de fractures et de chutes sont également disponibles. Enfin, de nombreuses études encourageantes sur l'efficacité de nouveaux traitements dans de multiples maladies osseuse rares, telles l'ostéogenèse imparfaite, la dysplasie fibreuse et l'hypoparathyroïdie, ont été publiées.

Bone loss after denosumab discontinuation is prevented by alendronate and zoledronic acid but not risedronate: a retrospective study.

A retrospective study of 121 patients who stopped denosumab (Dmab) then received no treatment (NT), risedronate (RIS), alendronate (ALN), or zoledronic acid (ZOL). Bone density (spine and hip) during and after Dmab discontinuation was measured. Treatment with ALN or ZOL, not NT and RIS, mitigated BMD loss after Dmab discontinuation. INTRODUCTION: Denosumab (Dmab) discontinuation is associated with bone loss and multiple vertebral fractures. The purpose was to compare bone mineral density (BMD) change in patients following Dmab discontinuation with no subsequent treatment (NT) and three bisphosphonate (BP) treatments: risedronate (RIS), alendronate (ALN), and zoledronic acid (ZOL). METHODS: In a review of 121 patients aged 71.2 ± 8.1 years, discontinuing Dmab (mean 5.4 doses), 33 received NT and 88 received BP (22 RIS; 34 ALN; 32 ZOL). BMD change after 1 year was compared between groups at the lumbar spine (LS), femoral neck (FN), and total hip (TH). Risk factors for bone loss after Dmab discontinuation were compared between groups and incidence of vertebral fractures was determined. RESULTS: Following Dmab discontinuation, LS mean change (g/cm2; 95% CI) was for NT: - 0.041 (- 0.062 to - 0.021); RIS: - 0.035 (- 0.052 to - 0.017); ALN: - 0.005 (- 0.020 to 0.009); and ZOL: - 0.009 (- 0.025 to 0.008). Differences in LS were found between NT and ALN (p =  0.015), and NT and ZOL (p=0.037), but not between NT and RIS. The only significant difference in TH was found between NT and ZOL (p 0.034) with no group differences in FN. BMD gains during Dmab treatment were associated with BMD loss after Dmab discontinuation. In a subset, discontinuation after Dmab treatment (> 5 doses) followed by ALN (n = 22) and ZOL (n = 11) showed no difference in BMD. Five of 7 vertebral fractures occurred after Dmab discontinuation in NT. CONCLUSION: Subsequent treatment with ALN or ZOL but not NT and RIS mitigates BMD loss after Dmab discontinuation.

Loss of lower extremity bone mineral density 1 year after denosumab is discontinued in persons with subacute spinal cord injury.

Twelve months following discontinuation of denosumab, the percent decrease in mean bone mineral density (BMD) values at the hip and knee regions were similar between both the denosumab and placebo groups. These findings emphasize the need for additional trials to understand the effect of continued administration of denosumab after subacute spinal cord injury (SCI) to avoid this demineralization. OBJECTIVE: To determine changes in BMD 1 year after denosumab was discontinued in participants with subacute SCI who had drug treatment initiated within 90 days post SCI and continued for 1 year. METHODS: Fourteen participants who completed a randomized, double-blinded, placebo-controlled drug trial (parent study: denosumab 60 mg (Prolia, Amgen Inc., n = 8) or placebo (n = 6); administered at baseline, 6, and 12 months) were followed 12 months after the 18 months from baseline primary end point was completed. The BMD of skeletal regions below the SCI at higher risk of fracture was measured [total hip, distal femur epiphysis (DFE), distal femur metaphysis (DFM), and proximal tibia epiphysis (PTE)] by dual energy X-ray absorptiometry. RESULTS: The percent decreases in mean BMD values at all regions of the hip and knee from 18 to 30 months were similar in both the denosumab and placebo groups. However, at 30 months, the absolute values for mean BMD remained significantly higher in the drug treatment than that of the placebo group at the DFM (p = 0.03), DFE (p = 0.04), and PTE (p = 0.05). CONCLUSIONS: In persons with SCI who initiated denosumab treatment during the subacute injury phase and maintained treatment for 1 year, the discontinuation of drug resulted in percent loss of mean BMD similar to that of the placebo group, with absolute mean BMD values at the knee regions at the 12-month follow-up visit significantly higher in the drug treatment than those in the placebo group. These data underscore the need to study continued administration of denosumab after subacute SCI to avoid marked demineralization in the sublesional skeleton upon discontinuation of this agent.

Discontinuation of denosumab in men with prostate cancer.

In patients with non-metastatic prostate cancer, treated with radiation therapy and androgen deprivation therapy for 3 years and DMAB on average for 5 years, BMD was in the normal or osteopenic range. Discontinuation of DMAB led to a bone loss of 2-5%. In men with osteopenia, the bone loss was prevented by zoledronate. PURPOSE: Patients with prostate cancer receiving androgen deprivation therapy (ADT) are treated with denosumab (DMAB) to prevent fractures and preserve bone mass. We wanted to investigate the change in BMD in men with non-metastatic prostate cancer discontinuing DMAB. METHODS: We conducted a retrospective cohort study based on medical records from patients referred to the Department of Endocrinology from the Department of Urology, Aarhus University Hospital between June 1, 2018, and June 1, 2021. We retrieved information on biochemistry and DXA performed 0-6 months after the last DMAB injection and a second DXA performed approximately 12 months after the first. In case of a BMD T-score ≤ - 1 at the lumbar spine or total hip at the first DXA, the patients were treated with zoledronate. The primary endpoint was change in lumbar spine BMD. RESULTS: We included 50 patients with non-metastatic prostate cancer. The mean DMAB treatment duration was 5 ± 0.1 years. Among the patients treated with zoledronate (n = 9), BMD was maintained at the spine and femoral neck after a mean of 16 months. We found a significant decrease in BMD; - 4.9 ± 4.2%, - 1.9 ± 3.5%, and - 2.4 ± 3.6% at the spine, total hip, and femoral neck between the first and second DXA in the patients not treated with zoledronate (n = 24) (p ≤ 0.01 for all). One patient who did not receive ZOL sustained multiple fragility vertebral fractures after DMAB discontinuation. CONCLUSION: In men with non-metastatic prostate cancer, discontinuation of DMAB after stopping ADT led to an average bone loss of 2-5%. Zoledronate prevented bone loss in men with osteopenia.

Anti-RANKL Therapy Prevents Glucocorticoid-Induced Bone Loss and Promotes Muscle Function in a Mouse Model of Duchenne Muscular Dystrophy.

Bisphosphonates prevent bone loss in glucocorticoid (GC)-treated boys with Duchenne muscular dystrophy (DMD) and are recommended as standard of care. Targeting receptor activator of nuclear factor kappa-B ligand (RANKL) may have advantages in DMD by ameliorating dystrophic skeletal muscle function in addition to their bone anti-resorptive properties. However, the potential effects of anti-RANKL treatment upon discontinuation in GC-induced animal models of DMD are unknown and need further investigation prior to exploration in the clinical research setting. In the first study, the effects of anti-RANKL and deflazacort (DFZ) on dystrophic skeletal muscle function and bone microstructure were assessed in mdx mice treated with DFZ or anti-RANKL, or both for 8 weeks. Anti-RANKL and DFZ improved grip force performance of mdx mice but an additive effect was not noted. However, anti-RANKL but not DFZ improved ex vivo contractile properties of dystrophic muscles. This functional improvement was associated with a reduction in muscle damage and fibrosis, and inflammatory cell number. Anti-RANKL treatment, with or without DFZ, also improved trabecular bone structure of mdx mice. In a second study, intravenous zoledronate (Zol) administration (1 or 2 doses) following 2 months of discontinuation of anti-RANKL treatment was mostly required to record an improvement in bone microarchitecture and biomechanical properties in DFZ-treated mdx mice. In conclusion, the ability of anti-RANKL therapy to restore muscle function has profound implications for DMD patients as it offers the possibility of improving skeletal muscle function without the steroid-related skeletal side effects.

Atypical antipsychotics olanzapine and clozapine increase bone loss in female rats with experimental periodontitis.

BACKGROUND AND OBJECTIVES: Periodontitis is a highly prevalent disease in psychiatric patients, including those undergoing symptomatic treatment with second-generation antipsychotics. Some of these drugs, such as clozapine (CLO) and olanzapine (OLA), have prominent metabolic effects such as weight gain, hyperglycemia, and dyslipidemia, which are risk factors for periodontitis. In addition to the metabolic effects, there are reports of changes in salivary flow, gingival bleeding, and caries. In this context, we aimed to evaluate if the metabolic effects of OLA and CLO alter periodontal parameters in an animal model of periodontitis without the environmental and psychosocial biases inherent to human diseases. METHODS: In the first set of experiments, male and female adult Wistar rats received oral administration of CLO, OLA, or vehicle for 45 days. They were evaluated for body mass composition and weight gain, blood glucose parameters (fasting and glucose tolerance and insulin resistance tests), and lipid profile (HDL, total cholesterol, and triglycerides). In a second set of experiments, the same measurements were performed in female rats exposed to the antipsychotics for 45 days and ligature-induced periodontitis on the 30th day of treatment. Macroscopic measurements of exposed roots, microtomography in the furcation region of the first molar, and histological evaluation of the region between the first and second molars were evaluated to assess bone loss. Additionally, gingival measurements of myeloperoxidase activity and pro-inflammatory cytokine TNF-α were made. RESULTS: Only females exposed to OLA had more significant weight gain than controls. They also exhibited differences in glucose metabolism. Ligature-induced periodontitis produced intense bone retraction without changing the density of the remaining structures. The bone loss was even higher in rats with periodontitis treated with OLA or CLO and was accompanied by a local increase in TNF-α caused by CLO. These animals, however, did not exhibit the same metabolic impairments observed for animals without periodontitis. CONCLUSION: The use of clozapine and olanzapine may be a risk factor for periodontal disease, independent of systemic metabolic alterations.

Safety and Efficacy of Alendronate to Treat Osteopenia in Children During Therapy for Acute Lymphoblastic Leukemia: A Retrospective Cohort Study of Sequential Outcomes.

BACKGROUND: Low bone mineral density is encountered in children with acute lymphoblastic leukemia (ALL) before, during, and after treatment. Prior experience with alendronate, an oral bisphosphonate, demonstrated high tolerability and evident clinical efficacy. However, concerns have been expressed about the long-term safety and utility of such agents in children. PROCEDURE: Sixty-nine children with ALL received alendronate for a mean of 87 weeks after dual-energy radiograph absorptiometry. Dual-energy radiograph absorptiometry was repeated following the completion of alendronate, and 5 to 9 years later in a subgroup of 32 children. Lumbar spine areal bone mineral density (LS aBMD) Z scores were obtained. RESULTS: The mean LS aBMD Z score rose from -1.78 to-0.47 ( P <0.0001). There was a modest median loss of LS aBMD subsequently in the 32 subjects on long-term follow-up. Almost 80% (N=172) of the children remain in continuous complete remission at a mean of 14.5 years from diagnosis. Of those who received alendronate, which was almost uniformly well tolerated, 7/69 (10.3%) relapsed compared with 19/89 (21.3%) who did not receive the drug. DISCUSSION: Alendronate appears to be well tolerated and moderately effective in osteopenic children with ALL. Whether it offers protection against relapse of leukemia needs further study.

The role of menopausal hormone therapy in the prevention and treatment of low bone density in perimenopausal and postmenopausal women.

PURPOSE OF REVIEW: The purpose of this review is to summarize the evidence on the benefits of menopausal hormone therapy (MHT) for the maintenance of skeletal health, prevention of osteoporosis and related fractures in peri and postmenopausal women. RECENT FINDINGS: We will review the impact of estrogen on skeletal health as well as the physiology of bone loss during the perimenopause and postmenopause. We will then elucidate the data that include estrogen alone and combination of MHT to demonstrate that in the absence of contraindication, MHT should be considered as an option for the maintenance of skeletal health both when concomitant menopausal symptoms are present and when not. SUMMARY: It has been well established that estrogens maintain bone mineral density (BMD) and reduce fracture risk at all sites. However, the most extensively studied form of estrogen with established fracture prevention is oral doses of synthetic estrogens. Due to the reduced risk profile, lower doses of bioidentical oral or transdermal estrogens are often preferred in clinical practice. We will highlight the current data on improvement in BMD and fracture risk reduction, including differences in formulation, dose, and route of delivery, to support a provider in the clinical decision-making process.

Health-related quality of life of men with primary osteoporosis and its changes after bisphosphonates treatment.

INTRODUCTION: Osteoporosis leads to more serious consequences in men than in women, but less is known about its impacts on health-related quality of life (HRQoL) of men, and whether the anti-osteoporosis treatment can improve HRQoL of men with osteopenia/osteoprosis. METHODS: We enrolled men with primary osteoporosis and age-matched healthy controls. We collected medical history, serum levels of carboxyl-terminal type I collagen telopeptide, procollagen type I propeptides, and bone mineral density of patients. All patients and controls completed the short-form 36 (SF-36) questionnaires. Changes in HRQoL of osteopenia/osteoporosis men were prospectively evaluated after alendronate or zoledronic acid treatment. RESULTS: A total of 100 men with primary osteoporosis or osteopenia and 100 healthy men were included. The patients were divided into three subgroups: osteopenia (n = 35), osteoporosis (n = 39) and severe osteoporosis (n = 26). Men with osteoporosis or severe osteoporosis had impaired HRQoL in domains of physical health compared to healthy controls. HRQoL scores in physical health related domains of patients with severe osteoporosis were significantly lower compared to healthy controls, and were the poorest among the three subgroups of patients. Fragility fracture history was correlated with lower SF-36 scores about physical health. In 34 men with newly diagnosed osteoporosis receiving bisphosphonates treatment, HRQoL scores were significantly improved in domains of physical health after treatments. CONCLUSIONS: The HRQoL is significantly impaired in men with osteoporosis, and the more severe the osteoporosis, the poorer the HRQoL. Fragility fracture is an important influencing factor of deteriorated HRQoL. Bisphosphonates treatment is beneficial to improve HRQoL of osteopenia/osteoporosis men.

The Effect of Preoperative Bisphosphonate Use on Total Hip Arthroplasty Outcomes.

BACKGROUND: Patients undergoing total hip arthroplasty (THA) commonly have osteoporosis for which bisphosphonates (BPs) are Food and Drug Administration (FDA)-approved for treatment. Bisphosphonate use post-THA is associated with decreased periprosthetic bone loss or revisions, and increased longevity of implants. However, evidence is lacking for preoperative bisphosphonate use in THA recipients. This study investigated the association between bisphosphonate use pre-THA and outcomes. METHODS: A retrospective review of a national administrative claims database was conducted. Among THA recipients who had a prior diagnosis of hip osteoarthritis and osteoporosis/osteopenia, the treatment group (BP-exposed) consisted of patients who had a history of bisphosphonate use at least 1 year before THA; controls (BP-naive) comprised patients who did not have preoperative bisphosphonate use. The BP-exposed were matched to BP-naive in a 1:4 ratio by age, sex, and comorbidities. Logistic regressions were used to calculate the odds ratio for intraoperative and 1-year postoperative complications. RESULTS: The BP-exposed group had significantly higher rates of intraoperative and 1-year postoperative periprosthetic fractures (odds ratio (OR): 1.39, 95% confidence interval (CI): 1.23, 1.57) and revisions (OR: 1.14, 95% CI: 1.04, 1.25) compared with the BP-naive controls. BP-exposed also experienced higher rates of aseptic loosening, dislocation, periprosthetic osteolysis, and stress fracture of the femur or hip/pelvis compared to the BP-naive controls, but these values were not statistically significant. CONCLUSION: The use of bisphosphonates in THA patients preoperatively is associated with higher rates of intraoperative and 1-year postoperative complications. These findings may impact the management of patients undergoing THA who have a prior diagnosis of osteoporosis/osteopenia and use of bisphosphonates. LEVEL OF EVIDENCE: Retrospective Cohort Study (Level 3).

Ibandronate Suppresses Changes in Apatite Orientation and Young's Modulus Caused by Estrogen Deficiency in Rat Vertebrae.

Bone material quality is important for evaluating the mechanical integrity of diseased and/or medically treated bones. However, compared to the knowledge accumulated regarding changes in bone mass, our understanding of the quality of bone material is lacking. In this study, we clarified the changes in bone material quality mainly characterized by the preferential orientation of the apatite c-axis associated with estrogen deficiency-induced osteoporosis, and their prevention using ibandronate (IBN), a nitrogen-containing bisphosphonate. IBN effectively prevented bone loss and degradation of whole bone strength in a dose-dependent manner. The estrogen-deficient condition abnormally increased the degree of apatite orientation along the craniocaudal axis in which principal stress is applied; IBN at higher doses played a role in maintaining the normal orientation of apatite but not at lower doses. The bone size-independent Young's modulus along the craniocaudal axis of the anterior cortical shell of the vertebra showed a significant and positive correlation with apatite orientation; therefore, the craniocaudal Young's modulus abnormally increased under estrogen-deficient conditions, despite a significant decrease in volumetric bone mineral density. However, the abnormal increase in craniocaudal Young's modulus did not compensate for the degradation of whole bone mechanical properties due to the bone loss. In conclusion, it was clarified that changes in the material quality, which are hidden in bone mass evaluation, occur with estrogen deficiency-induced osteoporosis and IBN treatment. Here, IBN was shown to be a beneficial drug that suppresses abnormal changes in bone mechanical integrity caused by estrogen deficiency at both the whole bone and material levels.

Anorexia Nervosa and Osteoporosis.

Patients with anorexia nervosa (AN) often experience low bone mineral density (BMD) and increased fracture risk, with low body weight and decreased gonadal function being the strongest predictors of the observed bone mineral deficit and fractures. Other metabolic disturbances have also been linked to bone loss in this group of patients, including growth hormone resistance, low insulin-like growth factor-1 (IGF-1) concentrations, low leptin concentrations, and hypercortisolemia. However, these correlations lack definitive evidence of causality. Weight restoration and resumption of menstrual function have the strongest impact on increasing BMD. Other potential treatment options include bisphosphonates and teriparatide, supported by data from small clinical trials, but these agents are not approved for the treatment of low BMD in adolescents or premenopausal women with AN.

The Effect of Anti-rheumatic Drugs on the Skeleton.

The therapeutic armamentarium for rheumatoid arthritis has increased substantially over the last 20 years. Historically antirheumatic treatment was started late in the disease course and frequently included prolonged high-dose glucocorticoid treatment which was associated with accelerated generalised bone loss and increased vertebral and non-vertebral fracture risk. Newer biologic and targeted synthetic treatments and a combination of conventional synthetic DMARDs prevent accelerated systemic bone loss and may even allow repair of cortical bone erosions. Emerging data also gives new insight on the impact of long-term conventional synthetic DMARDs on bone health and fracture risk and highlights the need for ongoing studies for better understanding of "established therapeutics". An interesting new antirheumatic treatment effect is the potential of erosion repair with the use of biologic DMARDs and janus kinase inhibitors. Although several newer anti-rheumatic drugs seem to have favorable effects on bone mineral density in RA patients, these effects are modest and do not seem to influence the fracture risk thus far. We summarize recent developments and findings of the impact of anti-rheumatic treatments on localized and systemic bone integrity and health.

Macromolecular Dexamethasone Prodrug Ameliorates Neuroinflammation and Prevents Bone Loss Associated with Traumatic Brain Injury.

Traumatic brain injury (TBI) is one of the leading causes of death and disability among children and young adults in the United States. In this manuscript, we assessed the utility of an N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-based dexamethasone (Dex) prodrug (P-Dex) in the treatment of TBI. Using a controlled cortical impact TBI mouse model, P-Dex was found to passively target and sustain at the traumatic/inflammatory brain tissue for over 14 days after systemic administration. The histological evidence supports P-Dex's therapeutic potential in ameliorating neuroinflammation and mitigating neurodegeneration. Behaviorally, the P-Dex-treated animals showed statistically significant improvement in balance recovery. A trend of neurological severity score improvement at the early time point post-TBI was also noted but did not achieve statistical significance. While probing the potential glucocorticoid side effects that may associate with P-Dex treatment, we discovered that the TBI mice develop osteopenia. Interestingly, the P-Dex-treated TBI mice demonstrated higher bone mineral density and better bone microarchitecture parameters when compared to free Dex and the saline control, revealing the osteoprotective effect of P-Dex in addition to its neuronal protection benefits post-TBI.

Influence of Moxonidine and Bisoprolol on Morphofunctional Condition of Arterial Wall and Telomerase Activity in Postmenopausal Women with Arterial Hypertension and Osteopenia. The Results from a Moscow Randomized Study.

PURPOSE: To compare the effect of 12 months of treatment with moxonidine or bisoprolol on telomerase activity (TA) and parameters characterizing the arterial wall state in postmenopausal women with arterial hypertension (AH) and osteopenia. METHODS: An open-label randomized study with 114 postmenopausal women with hypertension and osteopenia; pulse wave velocity (PWV), intima-media thickness (IMT), and TA were analyzed initially and after 12 months of therapy with moxonidine (n = 57) or bisoprolol (n = 57). RESULTS: Both medications effectively lowered blood pressure (BP) in both groups. After 12 months, the moxonidine group showed a significant increase in TA by 45.5% (from 0.87 to 1.15; p < 0.001), in contrast to the bisoprolol group, where TA decreased by 14.1% (from 0.89 to 0.74; p = 0.001). Within 12 months, in the moxonidine group, PWV decreased by 1.9% (from 10.35 ± 2.56 to 10.05 ± 2.29 m/s; p = 0.039), and in the bisoprolol group it increased by 5.8% (from 10.36 ± 2.47 to 11.26 ± 2.60 m/s; p < 0.001). In the moxonidine group, IMT increased by 3.5% on the right and 1.4% on the left, in the bisoprolol group - by 5.7% on the right and 4.2% on the left. CONCLUSION: A 12-month treatment with moxonidine but not with bisoprolol in postmenopausal women with AH and osteoporosis was associated with a decrease of arterial stiffness seen as statistically significantly reduced PVW and with increased TA.

Pediatric CKD-MBD: existing and emerging treatment approaches.

The effects of bone and mineral metabolism on skeletal formation, as well as vascular and soft tissue calcifications, define chronic kidney disease-metabolic bone disease (CKD-MBD). Treatment recommendations center on establishing adequate vitamin D status, phosphate control through diet restriction and phosphate binders, and the use of vitamin D analogs for specific indications. Several emerging bone-promoting therapies have now been studied in adults with CKD, including bisphosphonates and denosumab. These approaches are associated with improved bone mass and, in some cases, decreased fracture rates in adults with CKD-MBD and are of potential interest for some children with CKD-MBD. In children with CKD and immobilization and/or muscle weakness, bisphosphonates appear to be an effective treatment to increase bone mass; baseline assessment and careful monitoring of bone density and/or bone biopsy findings are important in consideration of any new bone therapies for children with CKD-MBD.