Decrease In Bone Turnover Markers Research Articles

Effect of denosumab treatment on bone mineral density and bone turnover markers in osteoporotic patients: real-life experience 2-year follow-up.

The long-term efficacy of anti-osteoclastic drugs in treatment of osteoporosis is well known. Denosumab, a novel human monoclonal antibody, is an anti-osteoclastic agent that has been shown to lead to reductions in vertebral, nonvertebral, and hip fracture risk in randomized and observational studies. Real-life data of this agent is increasing. In this study, we presented our real-life data about the 2-year follow-up of patients under denosumab treatment. Osteoporotic patients who were treated with at least one denosumab injection between 2014 and 2020years were included. Clinical and demographic data, bone turnover markers, and radiological reports (bone mineral densitometry (BMD), vertebral x-ray) were obtained from patient files retrospectively. A total of 305 patients (f/m: 275/30, 68.1 ± 11.05years) were included. The median injection number was 4 (1-10). Two hundred seventy-three patients (89.8%) were persistent on treatment at the 12th month; 175 patients (57.3%) were persistent at 24th month. Sixty-eight patients (22%) were not using denosumab anymore, 55 of the patients were not continuing by doctor desicion and 13 were not continuing due to patient-related causes. Median BMD levels significantly increased from 0.809 (0.2-1.601, IQR: 0.136) to 0.861 (0.517-1.607, IQR: 0.14) in L1-L4 and from 0.702 (0.349-0.997, IQR: 0.125) to 0.745 (0.508-1.008, IQR: 0.137) in femur area at the 24th month of treatment. An improvement of 8.04% in L1-L4 BMD and 4.5% in femur neck BMD levels at the 24th month of treatment was observed. There was a significant decrease in bone turnover markers at the 24th month of treatment. In our group of patients under denosumab treatment, 53% of persistence was found at 24months and associated with improvement in BMD levels without any significant side effects except one case with urticarial reaction. Denosumab leads to improvements in BMD levels and is a well-tolerated agent in a real-life setting comparable to results of randomized controlled studies in patients with different comorbidities.

Clinical study evaluating β-blockers use and fracture risk in patients with primary osteoporosis Running title

Background and objectives: In osteoporosis, low bone mass and growing fragility are main symptoms. BB users had greater BMD and/or decreased fracture risk, according to observational studies. Other studies found no effect of BB on fracture risk and osteoporosis disease. In this study, the effect of selective and non-selective BB on fracture risk in osteoporotic individuals was studied. Methods: A total of fifty osteoporotic patients of both genders were included in this randomized controlled, parallel, and prospective trial. Osteoporotic subjects were divided into three groups: a control group (CG), a non-selective beta-blocker group (NSBB), and a cardio-selective beta-blocker group (CSBB). T-score, fracture risk (FR), bone mineral density (BMD), and bone turnover markers were studied as a result of this investigation. Results: After six months of follow-up, it was discovered that the T-score mean values of the three groups varied significantly. BMD was significantly higher in the group receiving non-selective beta-blockers (NSBB) than in the control group (CG). In the three categories of fracture risk region, the fracture risk was statistically decreased in both the NSBB and CSBB groups. Additionally, both the NSBB and CSBB groups demonstrated a decrease in bone turnover markers (BTM), as contrasted to the control group.

A comparison of changes in bone turnover markers after gastric bypass and sleeve gastrectomy, and their association with markers of interest.

It is still debated whether differences in bone turnover markers (BTMs) exist between the 2 most popular bariatric surgery procedures (Roux-en-Y gastric bypass [RYGB] and sleeve gastrectomy [SG]). To compare changes in BTMs after RYGB and SG, and to investigate their association with predefined markers of interest. University hospital, Lille, France. An ancillary investigation of a prospective cohort was conducted. SG patients with severe obesity ≥40 years were matched one-to-one to RYGB patients for age, sex, body mass index (BMI), and menopausal status. BTMs, as well as predefined markers of interest, were measured at baseline, 12, and 24 months after bariatric surgery. Sixty-four patients (66% women) had a mean (standard deviation [SD]) age of 49.6 years (5.1) and a mean (SD) BMI of 45.0 kg/m2 (6.0). From baseline to 12 months, a significant increase in BTMs was observed in both groups (P < .001). Moreover, RYGB was associated with a greater increase in C-terminal telopeptide (β-CTX) and procollagen type 1 N-terminal propeptide (PINP) compared with SG (P < .0001). From 12 to 24 months, a significant decrease in BTMs was observed in both groups, but no significant differences were found between RYGB and SG. However, BTMs did not return to baseline levels. The changes in PINP and β-CTX at 12 months were independently associated with the type of surgical procedure, after adjusting for weight or each predefined marker of interest (all P < .0001). RYGB was associated with a greater increase in BTMs than SG at 12 and 24 months.

Biological therapy for osteoporosis - solving clinical problems - a case report

Introduction. Elucidation of the pathogenetic mechanisms of osteoporosis has led to the development of new and effective drugs from the group of biological agents. Case report. In April 2018, a 64-year-old female patient was presented to the hospital due to low back pain. She was diagnosed with postmenopausal osteoporosis based on bone density scan score and a compression fracture of the L1 vertebral body revealed by X-ray. She was treated with a weekly bisphosphonate and supplementation with vitamin D and calcium. After one year, monthly bisphosphonate was introduced in therapy because of an inadequate response. In April 2020, the patient was treated for COVID-19 according to protocol, and during the treatment, bisphosphonate therapy was discontinued. After five months, she suffered a fracture of her left forearm. Due to the persistence of low mineral bone density, which was complicated by a new fracture, denosumab 60 mg subcutaneously once every six months was initiated with additional vitamin D and calcium supplementation. At six months follow-up, an increase in mineral bone density was verified, and after 12 months, the dual-energy x-ray absorptiometry score was within the osteopenia range. Laboratory findings showed a decrease in bone turnover markers. Conclusion. One-year administration of denosumab led to a significant increase in bone mineral density measured at the lumbar spine and neck of the femur, as well as changes in the levels of biochemical markers of bone synthesis and resorption, and reduced the risk of new fractures.

Effects of diuretics furosemide and hydrochlorothiazide on CKD-MBD: A prospective randomized study

Although diuretics are often prescribed to control fluid overload, they can change Chronic kidney disease-mineral and bone disorder (CKD-MBD) parameters. Previous studies have shown an association between diuretic prescription and changes in both calciuria and parathormone levels. However, the causal relationship could not be confirmed. In addition, the effects of diuretics on bone mineral density and turnover markers are yet to be established. To evaluate the effects of diuretics on CKD-MBD, we have performed a prospective randomized trial comparing hydrochlorothiazide with furosemide in a stage 3CKD population followed for 1 year. Furosemide increased bone remodeling and parathormone levels, whereas hydrochlorothiazide attenuated parathyroid hormone rise and decreased bone turnover markers.

The Role of Bone Turnover Markers in the Follow up of the Treatment of Osteoporosis

Although bone mineral density (BMD) measurement is the common method for the diagnosis of postmenopausal osteoporosis (PMO, bone turnover markers have been proposed as good indicators for monitoring the efficiency of antiresorptive treatment. We aim to evaluate course of bone turnover markers in the follow-up of treatment osteoporosis and compare the results of these markers with bone mineral densities. 47 postmenopausal patients were included in this study. The age average of the patients was 59.1±7.6 (48-81). Patients were divided into 5 groups depending on the type of the treatment: Calcium and vitamin D (8 patients); calcium, vitamin D and risendronate (10 patients); calcium, vitamin D and alendronate (10 patients); calcium, vitamin D and hormone replacement therapy (tibolone) (9 patients) and calcium, vitamin D and calcitonine (10 patients). Samples were taken from each group, prior to treatment and in the third and sixth months of the treatment. Bone mineral density measurements were carried out before the treatment and in the sixth month. The basal concentrations of bone turnover markers [serum Type I collagen C-telopeptide (CTX), N-mid-Osteocalcin (OC) and urinary deoxypridinoline (Dpd)] and Interleukin-1b (IL-1b) were compared to the values in the third and sixth month of the therapy and also to BMD.OC, CTX and Dpd are good markers for the evaluation the effectiveness antiresorptive therapy. The changes in CTX and OC seems to be reflect the changes in bone mass in the early period. However, the changes in Dpd levels come out later. HRT (tibolone) and biphosphonates especially risendronate are thought to be effective therapeutic approaches, because a significant decrease in bone turnover markers and an improvement in BMD – especially in lombar vertebra - were observed in the follow up of treatment. A good correlation found between the changes in levels of CTX and Dpd and changes in BMD during treatment, which suggest that these two markers would be useful for monitoring response to antiresorptive therapy. Keywords: Postmenopausal osteoporosis, bone turnover markers, serum Type I collagen C-telopeptide, N-mid-Osteocalcin, urinary deoxypridinoline, Interleukin-1b DOI: 10.7176/JHMN/80-14 Publication date: September 30 th 2020

CApecitabine plus Radium-223 (Xofigo\u2122) in breast cancer patients with BONe metastases (CARBON): study protocol for a phase IB/IIA randomised controlled trial

BackgroundA substantial proportion of breast cancer patients develop metastatic disease, with over 450,000 deaths globally per year. Bone is the most common first site of metastatic disease accounting for 40% of all first recurrence and 70% of patients with advanced disease develop skeletal involvement.Treatment of bone metastases currently focusses on symptom relief and prevention and treatment of skeletal complications. However, there remains a need for further treatment options for patients with bone metastases. Combining systemic therapy with a bone-targeted agent, such as radium-223, may provide an effective treatment with minimal additional side effects.Methods/designCARBON is a UK-based, open-label, multi-centre study which comprises an initial safety phase to establish the feasibility and safety of combining radium-223 given on a 6-weekly schedule in combination with orally administered capecitabine followed by a randomised extension phase to further characterise the safety profile and provide preliminary estimation of efficacy.DiscussionThe CARBON study is important as the results will be the first to assess radium-223 with chemotherapy in advanced breast cancer. If the results find acceptable rates of toxicity with a decrease in bone turnover markers, further work will be necessary in a phase II/III setting to assess the efficacy and clinical benefit.Trial registrationISRCTN, ISRCTN92755158, Registered on 17 February 2016.

Leptin exerts a bone protective effect in ovariectomized rats by inhibiting osteoclastogenesis

Osteoporosis is one of the most prevalent bone diseases especially among postmenopausal women. The study was conducted on 36 female rats divided into three equal groups; i) Sham operated; ii) Ovariectomized (OVX) ; iii) Leptin treated ovariectomized. Serum receptor activator of nuclear factor κB ligand (RANKL) and osteoprotegerin (OPG), urinarydeoxypyridoline/creatinine (DPY)/Cr) were measured. The mRNA expression of RANKL and OPG were examined by real time polymerase chain reaction (PCR). Leptin decreased bone turnover markers and serum RANKL while it resulted in significant increase in serum Ca and OPG. Moreover, it had a significant anti-osteoporotic effect compared to OVX rats as it markedly down-regulated expression of RANKL and up-regulated expression of OPG in proximal femur, and thus lowered the RANKL/OPG ratio. These findings suggests that the anti-osteoporotic effect of leptin was by inhibiting osteoclastogenesis via modulating the RANKL/OPG ratio and that leptin can be used as alternative therapeutic agents of osteoporosis .

319. SWORD 1 and 2: Switch from TDF Containing Regimen to DTG+RPV Maintains Bone Mineral Density and Decreases Bone Turnover Markers Over 148 Weeks

BackgroundHIV infection and antiretroviral therapy (ART), particularly tenofovir (TDF), is associated with loss of bone mineral density (BMD). The SWORD studies demonstrated noninferiority of the 2-drug regimen (2DR) dolutegravir (DTG) + rilpivirine (RPV) to continuing current triple-therapy ART (CAR) at 48 weeks and continued viral suppression on DTG+RPV through Week 148. A substudy of SWORD 1 and 2 evaluated a change in BMD by DEXA for those participants who switched from triple ART containing TDF to DTG+RPV. The primary analysis reported at 48 weeks showed a significant increase in total hip and lumbar spine BMD and a significant decrease in bone turnover markers in patients receiving DTG+RPV compared with CAR. Here we present data through Week 148.MethodsHIV-infected adult patients with HIV-1 RNA < 50 c/mL received ART containing TDF for ≥6 months prior to randomization to DTG+RPV (Early Switch group, ES) or CAR on Day 1 (Baseline, BL) through Week 48 in SWORD-1/2. CAR patients suppressed at Week 48 switched to DTG+RPV at Week 52 (Late Switch group, LS). Hip and lumbar spine BMD were measured by DEXA scans read centrally. Secondary endpoints include a change in BMD and bone turnover markers through Week 148.ResultsFollowing switch to DTG+RPV significant increases were observed for total hip in the ES and LS groups through 100 weeks with a non-significant increase at Week 148 in ES (Figure 1a). Lumbar spine BMD significantly increased from BL at 48 weeks post switch, remained increased, though not significantly from BL through Week 148 (Figure 1b). The BMD of the LS group was similar to that of the ES group through 100 weeks exposure. The majority of patients remained in their pre-switch T-score category or improved a category for both hip and spine through Wk148 (Table 1). Through Wk148, BMI increased minimally and bone turnover markers significantly decreased (P < 0.001 to 0.042 across markers) from BL/LS BL except Type I Collagen C-Telopeptide at Wk148 in the LS group (P = 0.279).ConclusionSwitch to the DTG+RPV 2DR was associated with sustained improvements in BMD through Week 148, along with a reduction in bone markers. The favorable effects on skeletal health were observed despite the ageing of study patients and other factors decreasing BMD. A switch to DTG+RPV in suppressed patients provides a robust option for preserving bone health while continuing suppressive HIV treatment. Disclosures All authors: No reported disclosures.

Effects of ospemifene on bone in postmenopausal women

Ospemifene is a selective estrogen-receptor modulator approved for treating menopause-related moderate to severe dyspareunia and vaginal dryness, symptoms of vulvovaginal atrophy (VVA), in the United States, and for treating menopause-related, symptomatic VVA in women not appropriate for local estrogen therapy in Europe. This review summarizes the effects of ospemifene on bone, including bone biomarker data from a phase 3 vaginal dryness study. Early-phase studies of postmenopausal women showed that ospemifene dose-dependently decreased bone turnover markers versus placebo, similar to raloxifene. A 12-week, phase 3 study of ospemifene 60 mg/day in postmenopausal women showed improvements in all VVA parameters and significantly greater decreases in seven of nine bone biomarkers versus placebo. Lower bone resorption markers with ospemifene were observed regardless of time since menopause (≤5 years or >5 years) or baseline bone mineral density (BMD) (normal [n = 18], osteopenia [n = 164], or osteoporosis [n = 21]). Biomarker studies (n = 565 who took ospemifene) therefore support a potential role for ospemifene in maintaining bone health (and possibly reducing fracture risk) in postmenopausal women taking it for VVA; however, caution is warranted because data are limited to biochemical markers, rather than fracture and BMD. Although studies show that bone turnover predicts BMD and fractures, any hypothesis about a bone-sparing effect of ospemifene needs testing in rigorous, long-term, phase 3 studies monitoring fractures and BMD.

C-type natriuretic peptide attenuates renal osteodystrophy through inhibition of FGF-23/MAPK signaling

Renal osteodystrophy (ROD) occurs as early as chronic kidney disease (CKD) stage 2 and seems ubiquitous in almost all pediatric patients with CKD stage 5. Fibroblast growth factor (FGF)-23, a bone-derived endocrine regulator of phosphate homeostasis, is overexpressed in CKD and disturbs osteoblast differentiation and matrix mineralization. In contrast, C-type natriuretic peptide (CNP) acts as a potent positive regulator of bone growth. In the present study, we infused CNP into uremic rats and observed whether CNP could attenuate ROD through the inhibition of FGF-23 cascades. In uremic rats, CNP administration significantly alleviated renal dysfunction, calcium phosphate metabolic disorders, hypovitaminosis D, secondary hyperparathyroidism, the decrease in bone turnover markers and retarded bone pathological progression. More importantly, within FGF-23/mitogen-activated protein kinase (MAPK) signaling, the fibroblast growth factor receptor-1, Klotho and alternative (STAT-1/phospho-STAT-1) elements were upregulated by CNP, whereas FGF-23, RAF-1/phospho-RAF-1, and downstream (ERK/phospho-ERK and P38/phospho-P38) elements were paradoxically underexpressed in bone tissue. Therefore, CNP exerts a therapeutic effect on ROD through inhibition of FGF-23/MAPK signaling at the RAF-1 level.

Metformin decreases bone turnover markers in polycystic ovary syndrome: a post hoc study

To study the effects of metformin treatment on bone turnover in women with polycystic ovary syndrome (PCOS), as measured by serum concentrations of bone turnover markers. Post hoc study of a previously conducted prospective multicenter, placebo-controlled, randomized study. University clinic. The study cohort consisted of 74 non-obese women (body mass index < 27kg/m2) and 44 obese women (body mass index ≥ 27kg/m2) diagnosed with PCOS, with a mean age of 27.6 ± 4.0 (SD) years. Randomization to receive metformin or placebo for 3months. Serum levels of bone formation marker procollagen type I amino-terminal propeptide (PINP) and bone resorption marker carboxy-terminal cross-linking telopeptide of type I collagen (CTX) at baseline and after metformin/placebo treatment. Serum levels of PINP and CTX were similar between the metformin and placebo groups at baseline in the whole study population. Obese women, when compared with non-obese, had lower baseline levels of PINP and CTX. Levels of PINP and CTX were significantly reduced in the whole study population, as well as in both non-obese and obese women after 3months of metformin treatment, whereas no significant changes were observed in the placebo group. Metformin treatment, when compared with placebo, was associated with reduced bone turnover, as suggested by reductions in markers of bone formation and resorption, leading to slower bone remodeling in premenopausal women with PCOS. NCT00994812.

Effects of Vitamin D Supplementation on Bone Mineral Density and Bone Markers in HIV-Infected Youth.

Low bone mineral density (BMD) is a significant comorbidity in HIV. However, studies evaluating vitamin D supplementation on bone health in this population are limited. This study investigates changes in bone health parameters after 12 months of supplementation in HIV-infected youth with vitamin D insufficiency. This is a randomized, active-control, double-blind trial investigating changes in bone parameters with 3 different vitamin D3 doses [18,000 (standard/control dose), 60,000 (moderate dose), and 120,000 IU/monthly (high dose)] in HIV-infected youth 8-25 years old with baseline serum 25-hydroxyvitamin D (25(OH)D) concentrations <30 ng/mL. BMD and bone turnover markers were measured at baseline and 12 months. One hundred two subjects enrolled. Over 12 months, serum 25(OH)D concentrations increased with all doses, but the high dose (ie, 120,000 IU/monthly) maintained serum 25(OH)D concentrations in an optimal range (≥30 or ≥20 ng/mL) throughout the study period for more subjects (85% and 93%, respectively) compared with either the moderate (54% and 88%, respectively) or standard dose (63% and 80%, respectively). All dosing groups showed some improvement in BMD; however, only the high-dose arm showed significant decreases in bone turnover markers for both procollagen type 1 aminoterminal propeptide (-3.7 ng/mL; P = 0.001) and Β-CrossLaps (-0.13 ng/mL; P = 0.0005). High-dose vitamin D supplementation (120,000 IU/mo) given over 12 months decreases bone turnover markers in HIV-infected youth with vitamin D insufficiency, which may represent an early, beneficial effect on bone health. High vitamin D doses are needed to maintain optimal serum 25(OH)D concentrations.

Response of bone turnover markers to raloxifene treatment in postmenopausal women with osteopenia.

We used two methods of identifying women who reached the target for raloxifene treatment with bone turnover markers. Both approaches identified women that responded to treatment but did not fully agree and may be complementary. The change in bone turnover markers (BTMs) in response to osteoporosis therapy can be assessed by a decrease beyond the least significant change (LSC) or below the mean of the reference interval (RI). We compared the performance of these two approaches in women treated with raloxifene. Fifty postmenopausal osteopenic women (age 51-72years) were randomised to raloxifene or no treatment for 2years. Blood samples were collected for the measurement of BTM. The LSC for each marker was calculated from the untreated women and the RI obtained from healthy premenopausal women (age 35-40years). Bone mineral density (BMD) was measured at the spine and hip. There was a decrease in BTM in response to raloxifene treatment, percentage change at 12weeks: C terminal telopeptide of type I collagen (CTX) -39% (95% CI -48 to -28) and N terminal propeptide of type I procollagen (PINP) -32% (95% CI -40 to -23) P < 0.001. The proportion of women classified as responding to treatment using LSC at 12weeks was as follows: CTX 38% and PINP 52% and at 48weeks CTX 60% and PINP 65%. For the RI approach, the proportion of women classified as responding to treatment at 12 weeks was CTX and PINP 38 % and at 48 weeks CTX 40% and PINP 45%. There was a significant difference in the change in spine BMD in the raloxifene-treated group compared to the no-treatment group at week 48: difference 0.031g/cm(2) (95% CI 0.016 to 0.046, P < 0.001). The two approaches identified women that reached the target for treatment using BTM. Both LSC and RI criteria appear useful in identifying treatment response, but the two approaches do not fully overlap and may be complementary.

Stanozolol Decreases Bone Turnover Markers, Increases Mineralization, and Alters Femoral Geometry in Male Rats.

Stanozonol (ST) is a synthetic derivative of testosterone; it has anabolic/androgenic activity, increasing both the turnover of trabecular bone and the endocortical apposition of bone. The present study aimed to examine the effects of ST on bone status in rats by bone mineral content, markers of formation and resorption, bone density, and structural and microarchitectural parameters. Twenty male Wistar rats were randomly distributed into two experimental groups corresponding to placebo or ST administration, which consisted of weekly intramuscular injections of 10mg/kg body weight of ST. Plasma parameters were analyzed by immunoassay. Bone mineral content was determined by spectrophotometry. Bone mineral density (BMD) and structural parameters were measured by peripheral quantitative computed tomography, and trabecular and cortical microarchitecture by micro-computed tomography. Plasma Ca, Mg, and alkaline phosphatase were higher, and urinary Ca excretion, corticosterone, and testosterone concentrations lower in the ST group. Femur Ca content was higher and P content was lower in the ST, whereas osteocalcin, aminoterminal propeptides of type I procollagen, and C-terminal telopeptides of type I collagen were lower. Total cross-sectional, trabecular, and cortical/subcortical areas were lower in the ST. No differences were observed on BMD and area parameters of the diaphysis as well as on trabecular and cortical microarchitecture. The use of ST increases bone mineralization, ash percentage, and Ca and Mg content in femur. In spite of an absence of changes in BMD, geometric metaphyseal changes were observed. We conclude that ST alters bone geometry, leads to low bone turnover, and thus may impair bone quality.

Effect of Denosumab on Bone Mineral Density and Markers of Bone Turnover among Postmenopausal Women with Osteoporosis.

The aim of this study was to evaluate the effect of denosumab (Dmab) on bone mineral density (BMD) and bone turnover markers after 1 year of treatment. Additionally, the effect of Dmab in bisphosphonate-naïve patients (BP-naïve) compared to patients previously treated with bisphosphonates (BP-prior) was analyzed. This retrospective study included 425 postmenopausal women treated with Dmab for 1 year in clinical practice conditions in specialized centers from Argentina. Participants were also divided according to previous bisphosphonate treatment into BP-naïve and BP-prior. A control group of patients treated with BP not switched to Dmab matched by sex, age, and body mass index was used. Data are expressed as mean ± SEM. After 1 year of treatment with Dmab the bone formation markers total alkaline phosphatase and osteocalcin were significantly decreased (23.36% and 43.97%, resp.), as was the bone resorption marker s-CTX (69.61%). Significant increases in BMD were observed at the lumbar spine, femoral neck, and total hip without differences between BP-naïve and BP-prior. A better BMD response was found in BP-prior group compared with BP treated patients not switched to Dmab. Conclusion. Dmab treatment increased BMD and decreased bone turnover markers in the whole group, with similar response in BP-naïve and BP-prior patients. A better BMD response in BP-prior patients versus BP treated patients not switched to Dmab was observed.

Rhus javanica Gall Extract Inhibits the Differentiation of Bone Marrow-Derived Osteoclasts and Ovariectomy-Induced Bone Loss.

Inhibition of osteoclast differentiation and bone resorption is a therapeutic strategy for the management of postmenopausal bone loss. This study investigated the effects of Rhus javanica (R. javanica) extracts on bone marrow cultures to develop agents from natural sources that may prevent osteoclastogenesis. Extracts of R. javanica (eGr) cocoons spun by Rhus javanica (Bell.) Baker inhibited the osteoclast differentiation and bone resorption. The effects of aqueous extract (aeGr) or 100% ethanolic extract (eeGr) on ovariectomy- (OVX-) induced bone loss were investigated by various biochemical assays. Furthermore, microcomputed tomography (µCT) was performed to study bone remodeling. Oral administration of eGr (30 mg or 100 mg/kg/day for 6 weeks) augmented the inhibition of femoral bone mineral density (BMD), bone mineral content (BMC), and other factors involved in bone remodeling when compared to OVX controls. Additionally, eGr slightly decreased bone turnover markers that were increased by OVX. Therefore, it may be suggested that the protective effects of eGr could have originated from the suppression of OVX-induced increase in bone turnover. Collectively, the findings of this study indicate that eGr has potential to activate bone remodeling by inhibiting osteoclast differentiation and bone loss.

Bone health in cerebral palsy and introduction of a novel therapy.

ABSTRACTObjective To assess the bone health status of children with cerebral palsy and the therapeutic effect of denosumab in a subgroup of children with cerebral palsy and decreased bone mass.Methods Children with cerebral palsy were evaluated according to their motor disability score (classification system gross motor functions III to V), bone density and bone turnover markers. Dual X-ray energy absorption was used to measure the lumbar spine, and total body, except the head. Thereafter a group of children with cerebral palsy and osteoporosis was treated with denosumab, a fully human monoclonal antibody. Bone turnover markers were measured before and three months after treatment.Results Reduction in bone mineral density was observed, particularly in children with greater impairment evaluated by the motor score. Decreased bone turnover markers were found in a selected group of children three months after exposure to denosumab.Conclusion Bone loss was present in children with significant impairment of motor function, as well as decreased serum levels of bone resorption markers with new forms.

Differences in biochemical bone markers by diabetes type and the impact of glucose

BackgroundDiabetes mellitus is associated with an increased fracture risk, however the fracture risk is 7 fold increased in patients with type 1 diabetes (T1D) and 1.4 fold increased in patients with type 2 diabetes (T2D) with decreased and increased bone mineral density, respectively. Oral ingestion of glucose causes an acute decrease in bone turnover markers, and thus glucose levels may affect bone turnover in diabetes. ObjectiveThe aim was to examine disparities in bone turnover markers between patients with T1D and T2D and evaluate the effect of glucose on bone turnover. MethodsA cross-sectional study was conducted. Patients diagnosed with T1D (n=98) or T2D (n=96) were included from the outpatient clinics at two University Hospitals. All individuals had normal renal function. Glucose and bone turnover markers were measured in non-fasting blood samples. ResultsP-procollagen type 1 amino terminal propeptide (P1NP), p-osteocalcin (OC), and s-Receptor Activator of Nuclear factor Kappa beta Ligand (RANKL) were lower in patients with T2D compared to T1D, and s-osteoprotegerin (OPG) was higher in T2D. P-C-terminal cross-linked telopeptide of type-I collagen (CTX), p-fibroblast growth factor-23 (FGF-23), p-sclerostin, and p-undercarboxylated osteocalcin (ucOC) were similar in between the two groups of patients. Increasing non-fasting glucose levels were inversely related to p-CTX, p-P1NP, p-OC, and p-ucOC and directly related to s-OPG in simple linear and multiple linear regressions adjusted for factors influencing bone turnover markers including HbA1c. ConclusionBone turnover markers were lower in patients with T2D compared to T1D. Acute blood glucose alterations may change bone turnover mediated by OPG and have detrimental effects on bone health in diabetes.Trial registration number: ClinicalTrials.govNCT01870557.

Effects of switching weekly alendronate or risedronate to monthly minodronate in patients with rheumatoid arthritis: a 12-month prospective study.

Switching weekly ALN or RIS to monthly MIN in patients with RA, of whom two-thirds were treated with low-dose PSL, significantly decreased bone turnover markers and increased BMD at 12 months, suggesting that monthly MIN may be an effective alternative treatment option of oral bisphosphonate treatment. The aim of this prospective, observational study was to evaluate the effects of switching weekly alendronate (ALN 35 mg) or risedronate (RIS 17.5 mg) to monthly minodronate (MIN 50 mg) in patients with rheumatoid arthritis (RA). Patient characteristics were as follows: n = 172; 155 postmenopausal women, age 65.5 (44–87) years; T-score of lumbar spine (LS), −1.4; total hip (TH), −1.8; femoral neck (FN), −2.1; dose and rate of oral prednisolone (2.3 mg/day), 69.1 %; prior duration of ALN or RIS, 46.6 months; were allocated, based on their preference, to either the (1) continue group (n = 88), (2) switch-from-ALN group (n = 44), or (3) switch-from-RIS group (n = 40). After 12 months, increase in BMD was significantly greater in group 3 compared to group 1: LS (4.1 vs 1.2 %; P < 0.001), TH (1.9 vs −0.7 %; P < 0.01), and FN (2.7 vs −0.5 %; P < 0.05); and in group 2 compared to group 1: LS (3.2 vs 1.2 %; P < 0.05) and TH (1.5 vs −0.7 %; P < 0.01). The decrease in bone turnover markers was significantly greater in group 3 compared to group 1: TRACP-5b (−37.3 vs 2.5 %; P < 0.001), PINP (−24.7 vs −6.2 %; P < 0.05), and ucOC (−39.2 vs 13.0 %; P < 0.05); and in group 2 compared to group 1: TRACP-5b (−12.5 vs 2.5 %; P < 0.05) at 12 months. Switching weekly ALN or RIS to monthly MIN in patients with RA may be an effective alternative treatment option of oral bisphosphonate treatment.