Levels Of Bone Turnover Markers Research Articles

Comparison of the pleiotropic effect of atorvastatin and rosuvastatin on postmenopausal changes in bone turnover: A randomized comparative study.

Statins are the first-line treatment for dyslipidemia, which is a major modifiable risk factor for atherosclerotic cardiovascular disease. Studies have shown that in addition to the beneficial lipid-lowering effect, statins also exhibit a number of pleiotropic effects that may find application in other diseases, including osteoporosis. This study aimed to assess the effect of statins on bone turnover, as measured by the concentration of bone turnover markers, and to compare the effect of atorvastatin as a lipophilic statin and rosuvastatin as a hydrophilic statin. This study included 34 postmenopausal women aged < 65 years with newly diagnosed dyslipidemia requiring statin therapy. Patients were randomly assigned to receive a statin drug. Statins were initiated at standard doses of 5 to 10 mg of rosuvastatin and 20 mg of atorvastatin. The levels of C-terminal telopeptide of type I collagen as a bone resorption marker and N-terminal propeptide of procollagen type I as a marker of bone formation, lipid concentrations and other biochemical parameters were assessed at baseline and after 6 and twelve months of treatment. There were no statistically significant differences between the levels of bone turnover markers before and 6 months after statin implementation (P > .05) - for all patients or subgroups according to statin use. Analysis of the results showed that after 12 months, there was a statistically significant decrease in N-terminal propeptide of procollagen type I concentration in all subjects (P = .004). By statin subgroup, a statistically significant decrease in N-terminal propeptide of procollagen type I was observed only in patients receiving rosuvastatin (P = .012) and not in those receiving atorvastatin (P = .25). Moreover, changes in bone turnover markers did not correlate with changes in lipid concentrations. These results may indicate the superiority of atorvastatin over rosuvastatin in inhibiting adverse changes in bone turnover in postmenopausal women. Confirmed by studies involving a larger population, the observed differences might find particular applications in clinical practice, and the choice of atorvastatin over rosuvastatin for women could be considered in the early postmenopausal period to reduce the risk of osteoporosis and subsequent osteoporotic fractures.

Changes in serum bone turnover markers and bone mineral density Z-score in children with osteogenesis imperfecta after zoledronic acid treatment.

The study aimed to investigate the changes in the levels of serum bone turnover markers (BTMs) and bone mineral density (BMD) Z-score in pediatric patients with osteogenesis imperfecta (OI) after intravenous bisphosphonate therapy, and their association with age and estimated glomerular filtration rate (eGFR).This retrospective study analyzed data from 10 pediatric OI patients treated with intravenous zoledronic acid for over one year. Patients' clinical data were collected. The levels of bone turnover markers, and BMD Z-score before and after zoledronic acid treatment were analyzed. Significant improvement in BMD Z-score was observed after 6 and 12 months of treatment compared to baseline (all p < 0.05). The N-terminal propeptide of type I procollagen (PINP) levels decreased over time (all p < 0.05), indicating that zoledronic acid treatment decreased bone turnover. The levels of beta-C-terminal telopeptide of type I collagen (β-CTX) remained stable after treatment. No correlation was found between PINP level and age, eGFR, or BMD (all p > 0.05). Bisphosphonate treatment can improve BMD and decrease bone turnover (indicated by decrease levels of PINP) in pediatric OI patients. PINP may serve as an independent indicator for monitoring the efficacy of bisphosphonate treatment in pediatric OI patients, particularly in those under the age of 6, where standardized BMD Z-score criteria are lacking.

Circadian Regulation of Bone Remodeling.

Adult bones are continuously remodeled by the balance between bone resorption by osteoclasts and subsequent bone formation by osteoblasts. Many studies have provided molecular evidence that bone remodeling is under the control of circadian rhythms. Circadian fluctuations have been reported in the serum and urine levels of bone turnover markers, such as digested collagen fragments and bone alkaline phosphatase. Additionally, the expressions of over a quarter of all transcripts in bones show circadian rhythmicity, including the genes encoding master transcription factors for osteoblastogenesis and osteoclastogenesis, osteogenic cytokines, and signaling pathway proteins. Serum levels of calcium, phosphate, parathyroid hormone, and calcitonin also display circadian rhythmicity. Finally, osteoblast- and osteoclast-specific knockout mice targeting the core circadian regulator gene Bmal1 show disrupted bone remodeling, although the results have not always been consistent. Despite these studies, however, establishing a direct link between circadian rhythms and bone remodeling in vivo remains a major challenge. It is nearly impossible to repeatedly collect bone materials from human subjects while following circadian changes. In addition, the differences in circadian gene regulation between diurnal humans and nocturnal mice, the main model organism, remain unclear. Filling the knowledge gap in the circadian regulation of bone remodeling could reveal novel regulatory mechanisms underlying many bone disorders including osteoporosis, genetic diseases, and fracture healing. This is also an important question for the basic understanding of how cell differentiation progresses under the influence of cyclically fluctuating environments.

Diabetic Rats Induced Using a High-Fat Diet and Low-Dose Streptozotocin Treatment Exhibit Gut Microbiota Dysbiosis and Osteoporotic Bone Pathologies.

Type 2 diabetes mellitus (T2DM) presents a challenge for individuals today, affecting their health and life quality. Besides its known complications, T2DM has been found to contribute to bone/mineral abnormalities, thereby increasing the vulnerability to bone fragility/fractures. However, there is still a need for appropriate diagnostic approaches and targeted medications to address T2DM-associated bone diseases. This study aims to investigate the relationship between changes in gut microbiota, T2DM, and osteoporosis. To explore this, a T2DM rat model was induced by combining a high-fat diet and low-dose streptozotocin treatment. Our findings reveal that T2DM rats have lower bone mass and reduced levels of bone turnover markers compared to control rats. We also observe significant alterations in gut microbiota in T2DM rats, characterized by a higher relative abundance of Firmicutes (F) and Proteobacteria (P), but a lower relative abundance of Bacteroidetes (B) at the phylum level. Further analysis indicates a correlation between the F/B ratio and bone turnover levels, as well as between the B/P ratio and HbA1c levels. Additionally, at the genus level, we observe an inverse correlation in the relative abundance of Lachnospiraceae. These findings show promise for the development of new strategies to diagnose and treat T2DM-associated bone diseases.

Long-term Pegvisomant Therapy of Acromegaly: Effects on Bone Density, Turnover and Microstructure Using HRpQCT.

Fracture rate is increased in patients with active acromegaly and those in remission. Abnormalities of bone microstructure are present in patients with active disease and persist despite biochemical control after surgery. Effects of treatment with the GH receptor antagonist pegvisomant on bone microstructure were unknown. We studied 25 patients with acromegaly (15 men, 10 women). In 20, we evaluated areal bone mineral density (BMD) by dual-energy X-ray absorptiometry and bone turnover markers (BTMs) longitudinally, before and during pegvisomant treatment. After long-term pegvisomant in 17, we cross-sectionally assessed volumetric BMD, microarchitecture, stiffness, and failure load of the distal radius and tibia using high-resolution peripheral quantitative computed tomography (HRpQCT) and compared these results to those of healthy controls and 2 comparison groups of nonpegvisomant-treated acromegaly patients, remission, and active disease, matched for other therapies and characteristics. In the longitudinal study, areal BMD improved at the lumbar spine but decreased at the hip in men after a median ∼7 years of pegvisomant. In the cross-sectional study, patients on a median ∼9 years of pegvisomant had significantly larger bones, lower trabecular and cortical volumetric density, and disrupted trabecular microarchitecture compared to healthy controls. Microstructure was similar in the pegvisomant and acromegaly comparison groups. BTMs were lowered, then stable over time. In this, the first study to examine bone microstructure in pegvisomant-treated acromegaly, we found deficits in volumetric BMD and microarchitecture of the peripheral skeleton. BTM levels remained stable with long-term therapy. Deficits in bone quality identified by HRpQCT may play a role in the pathogenesis of fragility in treated acromegaly.

Dairy consumption, bone turnover biomarkers, and osteo sono assessment index in Japanese adults: A cross-sectional analysis of data from the Iwaki Health Promotion Project

PurposeDairy foods are nutritional sources of calcium, phosphorus, protein, and other nutrients that improve bone health. However, the effects of dairy consumption on bone biomarkers in the Japanese population remain unclear. This study explored the association between dairy consumption and bone biomarkers in Japanese adults. MethodsThis cross-sectional study was conducted as part of the Iwaki Health Promotion Project in Aomori, Japan. In total, 1063 adults were included in the analysis. Bone turnover marker levels were measured in local citizens during their annual medical checkups. The calcaneus osteo sono assessment index (OSI) was calculated using a quantitative ultrasound technique. The dietary intake of foods and nutrients was estimated using a food frequency questionnaire. Linear regression models were established using dairy consumption and bone biomarkers with adjustments. Statistic significance was considered by P < 0.05. ResultsIn multivariate models, the tartrate-resistant acid phosphatase 5b and parathyroid hormone concentrations were inversely associated with dietary dairy consumption after adjusting for age and sex. The undercarboxylated osteocalcin, a procollagen type I N-terminal peptide to bone alkaline phosphatase ratio, and OSI were the directly associated with dairy consumption in multivariate models with adjustment. ConclusionsDairy consumption is partially associated with bone turnover biomarkers and OSI in adult Japanese participants. Habitual consumption of dairy foods may contribute to the nutritional supplementation for maintaining bone health, including turnover and structure. Clinical trial registry number and website where it was obtainedThe Japanese Clinical Trials Registry (UMIN000040459), https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000046175.

Association between serum ferritin and bone turnover marker levels in type 2 diabetes mellitus patients with non-alcoholic fatty liver disease

ABSTRACT Objective To investigate the correlation between serum ferritin (SF) and bone turnover markers in type 2 diabetes mellitus (T2DM) patients with non-alcoholic fatty liver disease (NAFLD). Methods Seven hundred and forty-two people with T2DM were selected. Serum bone turnover markers: osteocalcin (OC), type I procollagen N-terminal peptide (PINP), β-I type collagen carboxy-terminal peptide (β-CTx), and 25-hydroxyvitamin D3 (25-[OH]-D) levels were detected. High SF (HF) was defined as the indicated SF levels above 400 ng/mL in males and more than 150 ng/mL in females. Patients were divided into four groups: T2DM+normal SF (non-HF); T2DM+high SF (HF); T2DM+NAFLD+non-HF; andT2DM+NAFLD+HF. Relationships between SF and bone turnover markers were analyzed. Results Compared with the T2DM+non-HF group, β-CTx levels were higher in the T2DM+HFgroup. Compared with the T2DM+NAFLD+non-HF group, β-CTx levels were increased and 25-(OH)-D levels decreased in the T2DM+NAFLD+HF group (all p < 0.05). SF was positively correlated with β-CTx [β = 0.074; 95% CI (0.003, 0.205)] and negatively correlated with 25-(OH)-D [β=-0.108; 95%CI (−0.006, −0.001)]. Compared with the T2DM+non-HF group, an independent positive correlation was found between β-CTx and SF in the T2DM+NAFLD+HF group [OR = 1.002; 95% CI (1.001, 1.004)]. Among males, SF was positively correlatedwith β-CTx [β = 0.114; 95% CI (0.031, 0.266)]. SF was negatively correlated with 25-(OH)-D levels in both male and female patients [β=-0.124; 95% CI (0.007,0.001) and β=-0.168; 95% CI (−0.012, −0.002)]. Among those >50 years of age and postmenopausal females, SF was negatively correlated with 25-(OH)-D levels [β=-0.117; 95% CI (−0.007, −0.001) and β=-0.003; 95% CI (−0.013, −0.003)]. Conclusion SF level was positively correlated with β-CTx in T2DM patients with NAFLD, which may promote bone resorption and increase the risk of bone loss.

Actigraphic sleep patterns are associated with bone turnover and bone mineral density among university students.

Poorer sleep is associated with poorer bone health among older adults but the role of sleep in bone health during younger adulthood is understudied. In this observational study, the averages and variability in total sleep time (TST), sleep efficiency (SE), and sleep midpoint of university students were examined in relation to levels of bone turnover markers (BTMs) and bone mineral density (BMD) at the lumbar spine and femur. A sample of healthy, university students (N = 59, aged 18-25 years, 51.8% female, body mass index <30 kg/m2 ), wore a wrist actigraph for 7 days, completed a dual-energy X-ray absorptiometry scan, and underwent blood sampling to assess serum BTM concentrations of osteocalcin (OC) and N-terminal telopeptide of type 1 collagen. A sub-sample (n = 14) completed a one-year follow-up. Multiple regression models examined the associations between each sleep metric and bone health outcome at baseline and 1-year follow-up. At baseline, greater variability in sleep midpoint was cross-sectionally associated with greater OC (β = 0.21, p = 0.042). In the exploratory, follow-up sub-sample, lower average TST (β = -0.66, p = 0.013) and SE (β = -0.68, p = 0.01) at baseline were associated with greater increases in OC at follow-up. Greater delays in mean sleep midpoint over follow-up were significantly associated with decreases in lumbar spine BMD (β = -0.49, p = 0.03). In a sample of young adults, variable sleep schedules were associated with greater bone turnover suggesting the potential importance of regular sleep for optimising bone health into early adulthood.

Nodakenin Ameliorates Ovariectomy-Induced Bone Loss by Regulating Gut Microbiota.

Disordered gut microbiota (GM) structure and function may contribute to osteoporosis (OP). Nodakenin has been shown to ameliorate osteoporosis; however, its anti-osteoporotic mechanism is unknown. This study aimed to further reveal the mechanism of the anti-osteoporotic action of nodakenin from the perspective of the microbiome and metabolome. An osteoporosis model was induced in mice through ovariectomy (OVX), with bone mass and microstructure assessed using μCT. Subsequently, ELISA and histologic examination were used to detect biochemical indicators of bone conversion and intestinal morphology. Using metabolomics and 16S rRNA sequencing, it was possible to determine the composition and abundance of the gut microbiota in feces. The results revealed that nodakenin treatment improved the bone microstructure and serum levels of bone turnover markers, and increased the intestinal mucosal integrity. 16S rRNA sequencing analysis revealed that nodakenin treatment decreased the relative abundance of Firmicutes and Patescibacteria, as well as the F/B ratio, and elevated the relative abundance of Bacteroidetes in OVX mice. In addition, nodakenin enhanced the relative abundance of Muribaculaceae and Allobaculum, among others, at the genus level. Moreover, metabolomics analysis revealed that nodakenin treatment significantly altered the changes in 113 metabolites, including calcitriol. A correlation analysis revealed substantial associations between various gut microbiota taxa and both the osteoporosis phenotype and metabolites. In summary, nodakenin treatment alleviated OVX-induced osteoporosis by modulating the gut microbiota and intestinal barrier.

Long-term effects of denosumab on bone mineral density and turnover markers in patients undergoing hemodialysis

IntroductionDenosumab, a fully human anti-RANKL monoclonal antibody, is a widely used osteoporosis treatment that is increasingly being used in patients undergoing dialysis; however, its long-term efficacy and safety in these patients remain unknown.Materials and methodsThis observational study comprised individuals aged ≥ 20 years undergoing hemodialysis and receiving denosumab. After denosumab administration, we analyzed the long-term changes in bone mineral density (BMD) and levels of bone turnover markers (BTMs) and calcium.ResultsThe study included 45 patients who have been receiving denosumab for a median duration of 3.8 (interquartile range, 2.5–6.7) years. Tartrate-resistant acid phosphatase 5b (TRACP-5b) levels decreased from a median of 595 (434–778) mU/dL at baseline to 200 (141–430) mU/dL after 6 months of denosumab administration (P < 0.001) and remained low thereafter. Similarly, bone-specific alkaline phosphatase (BAP) levels decreased from a median of 18.2 (15.9–25.8) μg/L at baseline to 12.4 (9.9–15.6) μg/L after 6 months (P < 0.001) and remained low thereafter. Meanwhile, BMD, as assessed with dual energy X-ray absorptiometry and measured at the distal 1/3 of the radius, did not decrease (0.465 ± 0.112 g/cm2 at baseline vs. 0.464 ± 0.112 g/cm2 after administration; P = 0.616). Regarding hypocalcemia, corrected calcium levels reached were the lowest at 7 days after administration and normalized within 30 days.ConclusionThe study showed long-term suppression of TRACP-5b and BAP levels and sustaining BMD after denosumab administration over an extended period in patients undergoing hemodialysis.

Osteoporosis and low bone mass among schizophrenia and bipolar disorder: A cross-sectional study with newly diagnosed, drug-naïve subjects

BackgroundA growing body of data shows that schizophrenia (SCZ) and bipolar disorder (BD) have substantial metabolic risks; however, few studies have focused on bone metabolism. This study aimed to assess the prevalence and associated influencing factors of low bone mass and osteoporosis in SCZ and BD before pharmacological effects occur. Methods108 healthy controls (HCs) and drug-naïve individuals with SCZ (n = 56) and BD (n = 130) had their lumbar spine (L1–L4) and left femur (Neck/Trochanter/Ward's triangle) bone mineral density (BMD) determined using dual-energy X-ray absorptiometry. Besides, we measured bone turnover markers (BTMs) levels, including procollagen I N-terminal propeptide, osteocalcin, and C-terminal cross-linking telopeptide of type I collagen in different groups. ResultsIndividuals with SCZ and BD had significantly lower BMD and significantly higher prevalence of low bone mass and osteoporosis compared with HCs. In the main observation regions of the total lumbar (F = 18.368, p < 0.001) and left femur (F = 14.790, p < 0.001), BMD was lower in individuals with SCZ and BD than HCs, with SCZ showing lower BMD than BD. The osteocalcin (H = 11.421, p = 0.003) levels were significantly higher in SCZ and BD than HCs.Binary regression analysis showed that SCZ or BD was an independent risk factor for low bone mass and osteoporosis. In addition, sex, age, and BTMs also influenced the occurrence of low bone mass and osteoporosis. LimitationsCross-sectional study. ConclusionThe results findings of the study might contribute to our understanding of the increased risk of bone metabolism in SCZ and BD. Clinical trial registrationwww.chictr.org.cn, identifier ChiCTR1900021379.

Effect of Tempeh and Daidzein on Calcium Status, Calcium Transporters, and Bone Metabolism Biomarkers in Ovariectomized Rats.

Menopause marks a critical life stage characterized by hormonal changes that significantly impact bone health, leading to a heightened susceptibility to bone fractures. This research seeks to elucidate the impact of daidzein and tempeh on calcium status, calcium transporters, and bone metabolism in an ovariectomized rat model. Forty female Wistar rats, aged 3 months, participated in a two-phase experiment. The initial phase involved inducing a calcium deficit, while the second phase comprised dietary interventions across five groups: Sham (S) and Ovariectomy (O) with a standard diet, O with bisphosphonate (OB), O with pure daidzein (OD), and O with tempeh (OT). Multiple parameters, encompassing calcium levels, calcium transporters, bone histopathology, and serum bone metabolism markers, were evaluated. The findings revealed that the OT group showcased heightened levels of bone turnover markers, such as pyridinoline, C-telopeptide of type I collagen, bone alkaline phosphatase, and procollagen type I N-terminal propeptide, in contrast to S and O groups, with statistical significance (p < 0.05). Histopathologically, both the OD and OT groups exhibited effects akin to the OB group, indicating a decrease in the surface area occupied by adipocytes in the femoral bone structure, although statistically non-equivalent, supporting the directionally similar trends. Although TRPV5 and TRPV6 mRNA expression levels in the jejunum and duodenum did not display statistically significant differences (p > 0.05), the OD and OT groups exhibited increased expression compared to the O group. We hypothesized that obtained results may be related to the effect of isoflavones on estrogen pathways because of their structurally similar to endogenous estrogen and weak estrogenic properties. In conclusion, the daily consumption of pure daidzein and tempeh could potentially improve and reinstate calcium status, calcium transport, and bone metabolism in ovariectomized rats. Additionally, isoflavone products demonstrate effects similar to bisphosphonate drugs on these parameters in ovariectomized rats.

Effect of Padzahr Tablet on Biochemical Indices of Bone Remodeling in Postmenopausal Females with Osteopenia: A Randomized Double-Blind Placebo-Controlled Trial

Background: Osteoporosis is a complex disease that poses major global public health challenges. Many individuals with osteoporosis turn to complementary and alternative medicine (CAM) for prevention and management. Due to its mineral contents, Padzahr, a type of clay used in traditional Persian medicine, is believed to have bone-forming properties. This study examined the impact of Padzahr on bone remodeling in postmenopausal women with low bone density.Materials and Methods: In this randomized double-blind and placebo-controlled clinical trial, 48 postmenopausal women with osteopenia were included. The participants were divided into two groups, with 24 participants in each group. One group received Padzahr, and the other group received a placebo. The participants took their assigned treatment for 12 weeks. Blood samples were taken from participants at the study’s beginning and end to compare the two groups’ serum levels of bone remodeling biomarkers.Results: At the outset of the study, the two groups were similar and there were no significant differences in any of the measured variables. Additionally, the levels of bone turnover markers were not significantly different between the two groups at the start of the study (P&gt;0.05). After 12 weeks of treatment, the results of the ANCOVA analysis showed no significant changes in the serum levels of bone turnover indices when comparing the Padzahr group to the placebo group (P&gt;0.05). Conclusion: A clinical trial of 3 months of Padzahr treatment in postmenopausal women with osteopenia did not show significant changes in serum markers of bone turnover.

Complex interplay of oral health, muscle and bone metabolism, and frailty in older individuals.

To investigate molecular and clinical background of associations among oral health, muscle and bone metabolism, and frailty incidence in patients with fall and fracture history. In total, 88 elderly participants (mean age 71.9 ± 5.8years) with the distal radius fractures were included. Participants were divided into three groups based on an Oral Health Assessment Tool score. Fried criteria and Mini-nutritional assessments were adopted to diagnose frailty and malnutrition, respectively. Blood samples were collected and analyzed for serum levels of bone turnover markers, proteins, insulin-like growth factor-1, 25-hydroxyvitamin D, and inflammatory cytokines. The mRNA levels of markers of inflammation, muscle synthesis and wasting, and muscle homeostasis regulator in the pronator quadratus muscle were analyzed. Patients with deteriorated oral health demonstrated a higher prevalence of frailty and malnutrition. Significantly lower serum levels of total protein and higher concentrations of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were detected in patients with poor oral health. Significant interaction effects between oral health and frailty level in gait speed, serum TNF-α, IL-1β, and total protein levels were exhibited. Significantly different mRNA expression levels in the pronator quadratus muscle of TNF-α, IL-1β, NF kB, MYOG, and FOXO1 following the oral health were detected. This study highlights relationship between oral health, nutritional uptake, systemic inflammation, and their combined impact on muscle and bone metabolism, ultimately affecting frailty development in the aging populations. A comprehensive understanding of mutual interactions among oral health, nutrition, and inflammation is essential for managing frailty.

Osteoking promotes bone formation and bone defect repair through ZBP1-STAT1-PKR-MLKL-mediated necroptosis.

Osteoking has been used for fracture therapy with a satisfying clinical efficacy. However, its therapeutic properties and the underlying mechanisms remain elusive. A bone defect rat model was established to evaluate the pharmacological effects of Osteoking by the dynamic observation of X-ray, micro-CT and histopathologic examination. Transcriptome profiling was performed to identify bone defect-related genes and Osteoking effective targets. Then, a "disease-related gene-drug target" interaction network was constructed and a list of key network targets were screened, which were experimentally verified. Osteoking effectively promoted bone defect repair in rats by accelerating the repair of cortical bone and the growth of trabeculae. Histopathologically, the bone defect rats displayed lower histopathologic scores in cortical bone, cancellous bone and bone connection than normal controls. In contrast, Osteoking exerted a favorable effect with a dose-dependent manner. The abnormal serum levels of bone turnover markers, bone growth factors and bone metabolism-related biochemical indexes in bone defect rats were also reversed by Osteoking treatment. Following the transcriptome-based network investigation, we hypothesized that osteoking might attenuate the levels of ZBP1-STAT1-PKR-MLKL-mediated necroptosis involved into bone defect. Experimentally, the expression levels of ZBP1, STAT1, PKR and the hallmark inflammatory cytokines for the end of necroptosis were distinctly elevated in bone defect rats, but were all effectively reversed by Osteoking treatment, which were also suppressed the activities of RIPK1, RIPK3 and MLKL in bone tissue supernatants. Osteoking may promote bone formation and bone defect repair by regulating ZBP1-STAT1-PKR axis, leading to inhibit RIPK1/RIPK3/MLKL activation-mediated necroptosis.

Rapid bone microarchitecture decline in older men with high bone turnover-the prospective STRAMBO study.

Older men with high bone turnover have faster bone loss. We assessed the link between the baseline levels of bone turnover markers (BTMs) and the prospectively assessed bone microarchitecture decline in men. In 825 men aged 60-87yr, we measured the serum osteocalcin (OC), bone alkaline phosphatase (BAP), N-terminal propeptide of type I procollagen (PINP), and C-terminal telopeptide of type I collagen (CTX-I), and urinary total deoxypyridinoline (tDPD). Bone microarchitecture and strength (distal radius and distal tibia) were estimated by high-resolution pQCT (XtremeCT, Scanco Medical) at baseline and then after 4 and 8yr. Thirty-seven men took medications affecting bone metabolism. Statistical models were adjusted for age and BMI. At the distal radius, the decrease in the total bone mineral density (Tt.BMD), cortical BMD (Ct.BMD), cortical thickness (Ct.Thd), and cortical area (Ct.Ar) and failure load was faster in the highest vs the lowest CTX-I quartile (failure load: -0.94 vs -0.31% yr-1, P < .001). Patterns were similar for distal tibia. At the distal tibia, bone decline (Tt.BMD, Ct.Thd, Ct.Ar, Ct.BMD, and failure load) was faster in the highest vs the lowest tDPD quartile. At each skeletal site, the rate of decrease in Tb.BMD differed between the extreme OC quartiles (P < .001). Men in the highest BAP quartile had a faster loss of Tt.BMD, Tb.BMD, reaction force, and failure load vs the lowest quartile. The link between PINP and bone decline was poor. The BTM score is the sum of the nos. of the quartiles for each BTM. Men in the highest quartile of the score had a faster loss of cortical bone and bone strength vs the lowest quartile. Thus, in the older men followed prospectively for 8yr, the rate of decline in bone microarchitecture and estimated bone strength was 50%-215% greater in men with high bone turnover (highest quartile, CTX-I above the median) compared to the men with low bone turnover (lowest quartile, CTX-I below the median).

Bone Metabolism in Men who Live with HIV Aged 50 years and Over: Impact of Infection Duration.

Early diagnosis and effective antiretroviral therapy (ART) lead to similar life expectancy in people living with HIV (PLWH) compared to the general population. This population faces problems such as decreased bone mineral density (BMD) and increased fracture risk. The aim of this study was to determine the prevalence of osteoporosis in men aged 50 years and over who were PLWH and to determine risk factors and changes in bone metabolism with bone turnover markers. 79 male PLWH aged 50 years and over were followed up in our outpatient clinic between May 2021 and October 2021. The patients' demographic, clinical, laboratory, and DEXA data were analyzed. Serum levels of bone turnover markers were measured. The prevalence of osteopenia, osteoporosis, and normal BMD was found to be 55.7%, 13.9%, and 30.4%, respectively. A correlation was found between low BMD and low body mass index, elapsed time since diagnosis of HIV infection, high rate of use of ART, and long usage time of tenofovir disoproxil fumarate + protease inhibitor. A one-year increase in HIV infection duration was associated with an increased risk of low BMD by 1.246. Compared to studies conducted on the general population, the prevalence of osteoporosis in male PLWH aged 50 years and older was two times higher. The limited effect of the duration of ART use on low BMD may be due to the patients' histories of replacement therapy. Therefore, to eliminate the negative effects of ART on BMD, it may be beneficial to start replacement therapy when necessary.

Extended Treatment With Recombinant Human Parathyroid Hormone (1-84) in Adult Patients With Chronic Hypoparathyroidism

ObjectiveRecombinant human parathyroid hormone (1-84) (rhPTH[1-84]) is efficacious in patients with hypoparathyroidism but additional data supporting its prolonged use are needed. We evaluated whether efficacy, safety, and tolerability are maintained during long-term rhPTH(1-84) treatment of patients with chronic hypoparathyroidism. MethodsThis was a phase 4, single-center, open-label, single-arm, 3-year extension (NCT02910466) of the phase 3 Hypo Extended (HEXT) study (NCT01199614). Patients self-administered rhPTH(1-84) once daily by subcutaneous injection, with doses individualized based on clinical parameters. Albumin-adjusted serum calcium levels (primary outcome measure), other disease biomarkers, health-related quality of life, and safety of rhPTH(1-84) were assessed using descriptive statistics. ResultsAll patients (n = 39) had been exposed to rhPTH(1-84) (mean exposure [SD] 8.5 [3.5] years) before the start of the study, resulting in a mean exposure of 10.8 years including the present study. Mean patient age was 51.9 years, 79.5% were female, and 97.4% were White. Mean albumin-adjusted serum calcium concentrations were within the target range, and mean serum phosphate, serum calcium-phosphate product, and 24-hour urinary calcium excretion levels were within reference ranges at end of treatment. Mean doses of supplemental calcium and active vitamin D were maintained throughout the study. Bone turnover marker levels were maintained from baseline to end of treatment. No clinically relevant changes in bone mineral density were observed. Patient-reported health-related quality-of-life scores were generally maintained throughout the study. Four adverse events were considered treatment related and no new safety signals were identified. ConclusionThe effects of rhPTH(1-84) on biochemical, skeletal, and health-related quality-of-life parameters did not wane with extended use.

High Incidence of Vitamin D Deficiency Among Patients Undergoing Hematopoietic Stem Cell Transplant and a Single Ultra-High Dose Vitamin D Replacement

Introduction: Vitamin D involves in several important human physiologic pathways from bone metabolism to inflammation and immune regulation. Patients who undergo hematopoietic stem cell transplant (HSCT) are at risk of developing vitamin D deficiency from various mechanisms and replacement of vitamin D in these patients can be challenging according to several reasons. In addition, vitamin D may potentially affect outcomes, overall health and quality of life after HSCT. An ultra-high dose vitamin D replacement was previously explored in pediatric HSCT patients but has never been investigated in adult patient population. In this study, we explored the incidence of vitamin D deficiency, the safety and efficacy of a single ultra-high dose vitamin D replacement including its effect on bone health among adult patients with hematologic malignancy undergoing HSCT. Patients and Methods: First, we looked at the retrospective cohort of patients who underwent HSCT between January 2017 and August 2022 to explore the incidence of vitamin D deficiency (25-hydroxy vitamin D level &amp;lt;20 ng/mL) in Thailand. Subsequently, we prospectively included adult patients with hematologic malignancy undergoing both autologous (ASCT) and allogeneic HSCT (alloHSCT) from September 2022 to June 2023. All patients received a single ultra-high dose vitamin D on the day of admission prior to the initiation of conditioning regimens. We reported the safety and efficacy of a single ultra-high dose vitamin D (Ergocalciferol; Vitamin D2) replacement as calculated by weight and pre-transplantation vitamin D level among these patients using the Stoss protocol previously described. The effect of an ultra-high dose vitamin D on bone turnover was also monitored. Results: In the retrospective cohort, 229 patients underwent HSCT (146 ASCT and 83 alloHSCT). Vitamin D deficiency was observed in 147 patients (64.6%) including 91 (62.3%) ASCT and 56 (67.5%) alloHSCT. The median 25-hydroxy (25-OH) vitamin D level was 17.6 (4.0-86.3) ng/mL comparable between autologous and allogeneic patients. In the prospective cohort, 45 patients underwent HSCT (27 ASCT and 18 alloHSCT). The median age of patients at the time of HSCT was 49 (23-67) years with 18 patients (40%) being male. The median pre-transplant 25-OH vitamin D level was 20.2 ng/mL with 22 patients (48.9%) (13 ASCT, 9 alloHSCT) meeting the criteria of vitamin D deficiency. The median dose of vitamin D2 used was 500,000 (300,000-600,000) IU. At day +28 post-HSCT, 40% of patients were able to attain 25-OH vitamin D level above 30 ng/mL comparable between ASCT and alloHSCT but significantly higher compared to the retrospective cohort. The time to neutrophil and platelet engraftment were 13 (9-26) days and 14 (9-33) days, comparable between the controlled retrospective cohort and high dose replacement prospective cohort. The median levels of parathyroid hormone (PTH) and bone turnover markers including osteocalcin, β-CrossLaps (β-CTx), and procollagen type I N-propeptide (PINP) at day+28 was 45.4 (19.4-152.2) pg/mL, 11.3 (6.0-16.8) ng/mL, 0.79 (0.1-13.0) ng/ml and 43.7 (19.7-133.7) mcg/L, respectively. Among patients who underwent alloHSCT, the incidence of cytomegalovirus reactivation and acute graft versus host disease was 72.2% and 11.1% (no grade 3-4), respectively. Figure 1 shows the kinetic of serum 25-OH vitamin D, Calcium, β-CTx and PINP of patients in the prospective cohort from baseline to day +28 post-HSCT. At all timepoints (day 0, +7, +14, +21, +28), the median level of vitamin D level was significantly higher whereas the median serum PINP level was significantly lower compared to the baseline level. There was no occurrence of hypercalcemia or bony events during the time of the study. Conclusion: Our study highlights a high incidence of vitamin D deficiency in HSCT patients. Utilizing a single ultra-high dose vitamin D is an effective and safe approach to replace vitamin D in adult patients undergoing HSCT. A high percentage of patients could maintain adequate vitamin D level during post-transplant period. PINP level was sustainably decreased after vitamin D replacement indicating a lower bone resorption. Whether this approach will translate into improved immune function, long-term bone health and outcomes compared to the conventional replacement strategy warrants further exploration in prospective randomized clinical trials.

Association of bone turnover markers and cognitive function in Chinese chronic schizophrenia patients with or without vitamin D insufficiency

BackgroundIncreasing evidence shows that bone turnover markers (BTMs) and vitamin D can affect human cognitive function. However, there are few studies that have investigated the association between BTMs and cognitive function in chronic schizophrenia patients. The aim of this study was to investigate the relationship between BTMs and cognitive function in chronic schizophrenia patients with or without vitamin D insufficiency (VDI).MethodsIn all, 118 chronic schizophrenia patients were enrolled in this cross-sectional study. Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was applied to evaluate the cognitive function of the subjects. Blood analysis included bone turnover markers, vitamin D levels, and glycolipid levels.ResultsRelative to 72 vitamin D-sufficient (VDS) patients, 46 VDI patients had higher bone resorption markers levels and lower bone formation markers levels. Regression analysis showed that, in the total sample, CTX and language function exhibited independent positive correlation (p = 0.027, R2 change = 0.042), and in the VDS group, procollagen type I N-terminal propeptide (PINP) was independently negatively correlated with language function (p = 0.031, R2 change = 0.065), while the positive correlation between osteopontin (OPN) and delayed memory remained in the VDI group (p = 0.036, R2 change = 0.083).ConclusionOur study showed an association between the levels of BTMs and cognitive function among chronic schizophrenia patients. This correlation may have different mechanisms of action at different vitamin D levels.