Clinical Utility of Bone Turnover Markers in Chronic Kidney Disease.

Chronic kidney disease (CKD) often leads to mineral and bone disorders (CKD-MBDs), which are nearly universal in patients undergoing dialysis. CKD-MBD includes abnormal calcium-phosphate metabolism, vascular and soft tissue calcification, and bone abnormalities (renal osteodystrophy [ROD]). Bone fragility in CKD occurs due to low bone mass and poor bone quality, and patients with CKD have higher fracture and mortality rates.

The relationship between baseline BMD and fracture incidence in the placebo groups of RCTs using individual patient data from the FNIH-ASBMR-SABRE Project.

We have proposed to the Food and Drug Administration (FDA) that treatment-related increases in total hip bone mineral density (TH BMD) at two years could be a surrogate endpoint for fracture risk reduction in clinical trials. The qualification of a surrogate includes a strong association of the surrogate with the clinical outcome. We compiled a large database of individual patient data (IPD) through the FNIH-ASBMR-SABRE project, and this analysis aimed to assess the relationship between baseline BMD and fracture risk in the placebo groups.

SB16 versus reference denosumab in postmenopausal women with osteoporosis: 18-month outcomes of a phase III randomized clinical trial.

Purpose: This study evaluated the efficacy, safety, pharmacodynamics (PD), pharmacokinetics (PK), and immunogenicity of SB16 versus reference denosumab (DEN) up to 18 months in postmenopausal osteoporosis (PMO) patients, and assessed outcomes after switching from DEN to SB16 compared to those who continued with DEN or SB16.

Methods: 457 PMO patients were initially randomized, with 407 re-randomized at Month 12 to either continue DEN (DEN+DEN), switch to SB16 (DEN+SB16), or continue SB16 (SB16 + SB16) through Month 18. Efficacy was assessed by the percent change from baseline in bone mineral density (BMD) at the lumbar spine, total hip, and femoral neck.

Estimating net bone formation relative to resorption using reference bone turnover markers.

Context: Individually, bone resorption or formation markers do not reflect bone balance.

Objective: 1) Combine reference bone resorption (collagen type I C-telopeptide, CTX) and formation (procollagen type I propeptide, PINP) markers to estimate balance by creating a bone balance index (BBI); 2) Examine associations of BBI, CTX, or PINP with bone mineral density (BMD) change.

Design: Mixed effects linear regression quantified associations of BBI, CTX, or PINP with BMD change rate.

The effects of denosumab on osteoclast precursors in postmenopausal women: a possible explanation for the overshoot phenomenon after discontinuation.

Upon denosumab discontinuation, an observed overshoot phenomenon in bone turnover may occur, potentially leading to a reduction in bone mineral density and the occurrence of vertebral fractures. Several theories have been proposed to explain this phenomenon, one of which is that osteoclast precursors might be accumulating during treatment. Our aim was to study the effects of denosumab on osteoclast precursors in postmenopausal women.

The Totality of Evidence for SDZ-deno: A Biosimilar to Reference Denosumab.

Purpose: Sandoz biosimilar denosumab (GP2411 [SDZ-deno]; Jubbonti/Wyost) is approved by the US FDA, EMA and Health Canada for all indications of reference denosumab (REF-deno; Prolia/Xgeva), a fully human IgG2κ monoclonal antibody that binds with high affinity and specificity to receptor activator of nuclear factor kappa-B ligand (RANKL). Denosumab blocks RANKL, preventing bone resorption and loss of bone density/architecture in conditions characterized by excessive bone loss such as osteoporosis in postmenopausal women and metastatic bone disease, among others.

Methods: This narrative review summarizes the totality of evidence (ToE) for SDZ-deno that supported its approval as Jubbonti/Wyost in the EU and US.

Effects of High Dose Bolus Cholecalciferol on Free Vitamin D Metabolites, Bone Turnover Markers and Physical Function.

High dose bolus cholecalciferol supplementation has been associated with falls and fracture, and this does not appear to be due to hypercalcaemia. The primary aim of this study was to determine the change in free vitamin D and metabolites after high dose bolus supplementation. This was a single centre, double-blinded, randomised, controlled trial of three different oral bolus doses of vitamin D (50,000 IU, 150,000 IU, and 500,000 IU) in otherwise healthy, vitamin D deficient (total 25-hydroxylated vitamin 25(OH)D < 30 nmol/L) postmenopausal women.

Associations of Serum GDF-15 Levels with Physical Performance, Mobility Disability, Cognition, Cardiovascular Disease, and Mortality in Older Adults.

Background: Growth differentiation factor 15 (GDF-15) is a member of the TGFβ superfamily secreted by many cell types and found at higher blood concentrations as chronological age increases (1). Given the emergence of GDF-15 as a key protein associated with aging, it is important to understand the multitude of conditions with which circulating GDF-15 is associated.

Methods: We pooled data from 1,174 randomly selected Health ABC Study (Health ABC) participants and 1,503 Cardiovascular Health Study (CHS) participants to evaluate the risk of various conditions and age-related outcomes across levels of GDF-15.

The relationship between treatment-related changes in total hip BMD measured after 12, 18, and 24 mo and fracture risk reduction in osteoporosis clinical trials: the FNIH-ASBMR-SABRE project.

There is a strong association between total hip bone mineral density (THBMD) changes after 24 mo of treatment and reduced fracture risk. We examined whether changes in THBMD after 12 and 18 mo of treatment are also associated with fracture risk reduction. We used individual patient data (n = 122 235 participants) from 22 randomized, placebo-controlled, double-blind trials of osteoporosis medications.

The impact of androgen deprivation therapy on bone microarchitecture in men with prostate cancer: A longitudinal observational study (The ANTELOPE Study).

Introduction: Androgen Deprivation Therapy (ADT) for prostate cancer (PC) has substantial negative impacts on the musculoskeletal system and body composition. Many studies have focused on the effects of ADT on areal bone mineral density (aBMD), but aBMD does not capture key determinants of bone strength and fracture risk, for example volumetric bone density (vBMD), geometry, cortical thickness and porosity, trabecular parameters and rate of remodelling. More specialist imaging techniques such as high-resolution peripheral quantitative computed tomography (HR-pQCT) have become available to evaluate these parameters.

Once-weekly semaglutide versus placebo in adults with increased fracture risk: a randomised, double-blinded, two-centre, phase 2 trial.

Background: Previous studies have indicated that glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) may enhance bone formation and have neutral or beneficial effects on fracture risk. We evaluated the effect of the GLP-1RA semaglutide on the bone formation marker Procollagen type I N-terminal propeptide (PINP) in adults with increased fracture risk.

Methods: This randomised, placebo-controlled, double-blinded, phase 2 clinical trial was conducted at two public hospitals in Denmark.

Pre-treatment bone mineral density and the benefit of pharmacologic treatment on fracture risk and BMD change: analysis from the FNIH-ASBMR SABRE project.

Some osteoporosis drug trials have suggested that treatment is more effective in those with low BMD measured by DXA. This study used data from a large set of randomized controlled trials (RCTs) to determine whether the anti-fracture efficacy of treatments differs according to baseline BMD. We used individual patient data from 25 RCTs (103 086 subjects) of osteoporosis medications collected as part of the FNIH-ASBMR SABRE project.

Prolonged bone health benefits for breast cancer patients following adjuvant bisphosphonate therapy: the BoHFAB study.

Adjuvant bisphosphonates are often recommended in postmenopausal women with early breast cancer at intermediate-to-high risk of disease recurrence, but the magnitude and duration of their effects on bone mineral density (BMD) and bone turnover markers (BTMs) are not well described. We evaluated the impact of adjuvant zoledronate on areal BMD and BTMs in a sub-group of patients who had completed the large 5-yr randomized Adjuvant Zoledronic Acid to Reduce Recurrence (AZURE) trial. About 224 women (recurrence free) who had completed the AZURE trial within the previous 3 mo were recruited from 20 UK AZURE trial sites.

Week-by-week changes in serum levels of bone-related circulating microRNAs and bone turnover markers.

MicroRNAs are involved in post-transcriptional regulation of gene expression. Due to their regulatory role, microRNAs are differently expressed during specific conditions in healthy and diseased individuals, so microRNAs circulating in the blood could be used as diagnostic and prognostic biomarkers for various diseases and conditions. We want to investigate the variability of circulating microRNAs and bone turnover markers in weekly time intervals in older women.

Equivalence trial of proposed denosumab biosimilar GP2411 and reference denosumab in postmenopausal osteoporosis: the ROSALIA study.

Denosumab is a monoclonal antibody used to reduce risk of fractures in osteoporosis. ROSALIA was a multicenter, double-blind, randomized, integrated phase I/phase III study comparing the efficacy, pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, and safety of proposed biosimilar denosumab GP2411 with reference denosumab (REF-DMAb) (Prolia®; Amgen). Postmenopausal women with osteoporosis were randomized 1:1 to 2 60-mg doses of GP2411 or REF-DMAb, one at study start and one at week 26.

Bone remodeling and responsiveness to mechanical stimuli in individuals with type 1 diabetes mellitus.

Type 1 diabetes mellitus (T1DM) has been linked to increased osteocyte apoptosis, local accumulation of mineralized lacunar spaces, and microdamage suggesting an impairment of the mechanoregulation network in affected individuals. Diabetic neuropathy might exacerbate this dysfunction through direct effects on bone turnover, and indirect effects on balance, muscle strength, and gait. However, the in vivo effects of impaired bone mechanoregulation on bone remodeling in humans remain underexplored.

DXA-based statistical models of shape and intensity outperform aBMD hip fracture prediction: A retrospective study.

Areal bone mineral density (aBMD) currently represents the clinical gold standard for hip fracture risk assessment. Nevertheless, it is characterised by a limited prediction accuracy, as about half of the people experiencing a fracture are not classified as at being at risk by aBMD. In the context of a progressively ageing population, the identification of accurate predictive tools would be pivotal to implement preventive actions.

Efficacy of Osteoporosis Medications in Patients with Type 2 Diabetes.

Purpose Of The Review: The purpose of the review is to summarise the current scientific evidence on the efficacy of osteoporosis medications in patients with type 2 diabetes.

Recent Findings: Type 2 diabetes (T2D) is a growing global epidemic. The highest prevalence is observed in the elderly, the same population affected by osteoporosis.

Changes in Collagen Type I C-Telopeptide and Procollagen Type I N-Terminal Propeptide During the Menopause Transition.

Context: Collagen type I C-telopeptide (CTX) and procollagen type I N-terminal propeptide (PINP) are reference bone resorption and formation markers, respectively.

Objective: To characterize CTX and PINP trajectories across the menopause transition (MT).

Methods: This 18-year longitudinal analysis of a community-based cohort from the Study of Women's Health Across the Nation included 541 women (126 Black, 90 Chinese, 87 Japanese, 238 White) who transitioned from pre- to postmenopause.

Sex- and Age Group-Specific Fracture Incidence Rates Trends for Type 1 and 2 Diabetes Mellitus.

The incidence of major osteoporotic fractures has declined in men and women in Western countries over the last two decades. Although fracture risk is higher in persons with diabetes mellitus, trends of fractures remain unknown in men and women with diabetes. We investigated the trends in fracture incidence rates (IRs) in men and women with type 1 diabetes mellitus (T1D) and type 2 diabetes mellitus (T2D) in Denmark between 1997 and 2017.