Levels Of Bone Turnover Markers Research Articles

Antiosteoporosis and bone protective effect of alpinumisoflavone in steroid-induced osteoporosis rats via alteration of apoptosis, inflammatory and RANK/RANKL/OPG signaling pathway

Objective: To estimate the bone protective effect of alpinumisoflavone, a natural prenylated isoflavonoid, against glucocorticoid-induced osteoporosis in rats. Methods: Male Wistar rats received intramuscular administration of dexamethasone (4 mg/mL) at a dose level of 7 mg/kg for 5 weeks, and then alpinumisoflavone (5, 10, and 15 mg/kg) and alendronate (2 mg/kg) from 2 weeks. The body weight and organ weight (femoral, vagina, and uterus) were estimated. MicroCT analysis, bone turnover markers, bone parameters, oxidative stress parameters, and inflammatory cytokines were estimated. mRNA expressions of related genes were also estimated. Results: Alpinumisoflavone remarkably boosted body weight and organ weight (ureters and vagina), improved microCT analysis parameters, and boosted levels of bone markers. Besides, alpinumisoflavone considerably (P<0.001) restored the level of bone turnover markers and oxidative stress parameters, remarkably suppressed the level of cytokines such as interleukin-1β, interleukin-6, tumor necrosis factor-α, and increased transforming growth factor-β and insulin-like growth factor. It also significantly restored the osteoprotegerin (OPG, RANKL, and OPG/RANKL ratio) levels and the mRNA expression of Caspase (3, 6, 7, 9), BMPs, OPN, ALP, RUNX2, and OCN. Conclusions: The current result suggests the bone protective effect of alpinumisoflavone against glucocorticoid-induced osteoporosis in rats.

Comparison of bone turnover suppression in atypical femoral fractures and osteoporotic hip fractures

We aimed to compare the extent of bone turnover suppression between patients with atypical femoral fractures (AFFs) and osteoporotic hip fractures (typical femur fractures, TFFs) using a one-to-one matching strategy. A single-center retrospective comparison of females aged ≥ 60 years who underwent operative treatment for AFFs and TFFs between January 2010 and March 2021 was conducted. Demographic characteristics and clinical data including fracture site, past medical history, bone mineral density (BMD), bisphosphonate (BP) medication history, and serum bone turnover marker (BTM) levels were examined. Moreover, we performed a logistic regression analysis to determine the risk factors for AFFs and a one-to-one matched-pair analysis to compare various BTMs. Overall, 336 consecutive females were included: 113 with AFFs and 213 with TFFs. The mean age, BMI, and lowest BMD T-score were 78.6 years, 22.8 kg/m2, and −3.3, respectively. Patients with AFF were younger, had lower BMD, higher BMI, higher prevalence of rheumatoid arthritis, a greater proportion with previous steroid or BP use, and a longer history of BP use than patients with TFF. The 48:48 matched-pair analysis revealed higher serum 25(OH) vitamin-D (30.5 vs 18.2 ng/mL, P < 0.001) and calcium levels (8.8 vs 8.3 ng/dL, P = 0.009) and lower serum CTX levels (0.33 vs 0.54 ng/mL, P = 0.010) in the AFF group than in the TFF group, suggesting a more suppressed bone remodeling. No differences in the other BTM levels were found. Despite identical histories and durations of BP use, the AFF group exhibited lower CTX levels, suggesting more suppressed bone remodeling. This observation leads us to infer that more suppressed bone remodeling, indicated by lower CTX levels, could be linked to the occurrence of AFFs.

Mir-381-3p aggravates ovariectomy-induced osteoporosis by inhibiting osteogenic differentiation through targeting KLF5/Wnt/β-catenin signaling pathway

BackgroundIncreasing evidence shows the pivotal significance of miRNAs in the pathogenesis of osteoporosis. miR-381-3p has been identified as an inhibitor of osteogenesis. This study explored the role and mechanism of miR-381-3p in postmenopausal osteoporosis (PMOP), the most common type of osteoporosis.MethodsBilateral ovariectomy (OVX) rat model was established and miR-381-3p antagomir was administrated through the tail vein in vivo. The pathological changes in rats were assessed through the evaluation of serum bone turnover markers (BALP, PINP, and CTX-1), hematoxylin and eosin (H&E) staining, as well as the expression of osteoblast differentiation biomarkers. Moreover, isolated bone marrow mesenchymal stem cells from OVX-induced rats (OVX-BMMSCs) were utilized to explore the impact of miR-381-3p on osteoblast differentiation. In addition, the target gene and downstream pathway of miR-381-3p were further investigated both in vivo and in vitro.ResultsmiR-381-3p expression was elevated, whereas KLF5 was suppressed in OVX rats. miR-381-3p antagomir decreased serum levels of bone turnover markers, improved trabecular separation, promoted osteoblast differentiation biomarker expression in OVX rats. ALP activity and mineralization were suppressed, and levels of osteoblast differentiation biomarkers were impeded after miR-381-3p overexpression during osteoblast differentiation of OVX-BMMSCs. While contrasting results were found after inhibition of miR-381-3p. miR-381-3p targets KLF5, negatively affecting its expression as well as its downstream Wnt/β-catenin pathway, both in vivo and in vitro. Silencing of KLF5 restored Wnt/β-catenin activation induced by miR-381-3p antagomir.ConclusionmiR-381-3p aggravates PMOP by inhibiting osteogenic differentiation through targeting KLF5/Wnt/β-catenin pathway. miR-381-3p appears to be a promising candidate for therapeutic intervention in PMOP.

Efficacy and safety of minodronate in the treatment of postmenopausal osteoporosis with low back pain: a single-centre, randomized and open-label controlled trial

BackgroundLow back pain is one of the most common symptoms of osteoporosis. The pain can seriously affect patients’ mood and quality of life; it can also further aggravate bone loss, causing a serious social burden. Minodronate is an oral bisphosphonate that needs to be administered daily. It significantly reduces levels of bone turnover markers (BTMs) and rapidly improves symptoms of low back pain in patients with osteoporosis. Osteoporosis requires long-term treatment, and daily dosing reduces patient compliance. Minodronate has a better safety profile than other bisphosphonates. The objective of the trial is to explore the efficacy and safety of minodronate in the treatment of low back pain in postmenopausal osteoporosis patients.MethodsThis is a single-centre, randomized, open-label controlled trial with a 24-week duration. Seventy-two eligible patients will be randomly divided into 4 groups. Subjects will be randomized at a 1:1 ratio to receive either minodronate (1 mg/day) or alendronate (10 mg/day) every day; senior women (≥ 75 years old) and older women (< 75 years old) will be at a ratio of 1:2. The primary outcome is the time required for the visual analogue scale (VAS) score to decline by ≥ 10 from baseline. The secondary outcome is the changes in VAS scores from baseline, the frequency and dosage of rescue medication, BTMs, bone mineral density (BMD), and variations in upper gastrointestinal (GI) symptom scores from baseline (including heartburn, pain, and bloating).DiscussionThis study will provide objective evidence for the efficiency and safety of minodronate. Furthermore, it will be helpful to evaluate the quantitative relationship between BTMs and BMD in patients with osteoporosis under different ages.Trial registrationThis study protocol has been registered with ClinicalTrials.gov ID NCT05645289 (https://clinicaltrials.gov/search?term=NCT05645289) on December 8, 2022. The registry name is Peking University Third Hospital. This study protocol was reviewed and approved by the Peking University Third Hospital Medical Science Research Ethics Committee (M2022465, 2022.08.09, V2.0). The results will be published in scientific peer-reviewed journals.Trial statusThe protocol was registered at ClinicalTrials.gov (registration number: NCT05645289). Recruitment has started in January 2023 and is still ongoing.

One versus 2years of alendronate following denosumab: the CARD extension.

When denosumab is discontinued, antiresorptive therapy is critical to attenuate high-turnover bone loss. The ideal choice and duration of antiresorptive therapy are not yet defined, however. In the Comparison of Alendronate or Raloxifene following Denosumab (CARD) study, we demonstrated that 12months of alendronate was better able to maintain the bone mineral density (BMD) gains achieved with 12months of denosumab versus 12months of raloxifene. In this extension, we wished to determine if 12months of alendronate would be sufficient in maintaining these denosumab-induced BMD gains. In the CARD study, postmenopausal osteoporotic women aged 60-79 at high fracture risk received 12months of denosumab 60-mg SC every 6months followed by 12months of either alendronate 70mg weekly (N = 26) or raloxifene (N = 25). All subjects in the alendronate arm were then offered participation in a 1-year extension in which they were randomized to continue alendronate for an additional 12months (N = 10) or to receive calcium and vitamin D alone (N = 8). The primary outcome was change in spine BMD between months 24 and 36. Exploratory endpoints included changes in areal BMD (aBMD) at other anatomic sites as well as changes in serum bone turnover markers. The CARD study demonstrated the effectiveness of 12months alendronate in preserving denosumab-induced BMD gains. In the extension, aBMD was maintained at the spine, total hip, and femoral neck in both those randomized to an additional year of alendronate and those randomized to calcium/vitamin D alone. We did, however, observe a transient comparative decrease between months 24-30 in the calcium/vitamin D group at the total hip (P = 0.008) and femoral neck (P = 0.040). At the end of 24months of the CARD study, bone turnover markers serum c-telopeptide (CTX) and procollagen N-propeptide of type I collagen (PINP) were suppressed in both groups and then increased more between months 24-36 in the calcium/vitamin D group than the alendronate group (P = 0.051 for CTX, P = 0.030 for P1NP). Both CTX and PINP remained below the month 0 baseline in both groups (P < 0.05 for all comparisons). With the limitations of our small sample size, these data suggest that both 1 and 2years of alendronate effectively maintain BMD gains achieved with 1year of denosumab and prevented any rebound in bone turnover marker levels above pre-denosumab baseline. This is the first randomized trial to assess minimum duration of bisphosphonate after short-term denosumab and may be helpful to guide clinical care. Similar studies performed after longer durations of denosumab would be helpful to further define optimal management. ClinicalTrials.gov registration number: NCT03623633.

Can a 6-Month Exercise Training Program Improve Musculoskeletal Health in Individuals with Systemic Lupus Erythematosus post Glucocorticoid Pulsetherapy? Protocol for a Randomized Controlled Trial

ABSTRACT Background Systemic lupus erythematosus is an autoimmune condition characterized by immune dysregulation, exacerbated systemic inflammation, and tissue damage. Glucocorticoid (GC) pulse therapy is a pharmacological strategy used to manage high activity phases. Although clinically effective, it can lead to adverse effects, including compromised musculoskeletal health. Adjuvant therapies that allow maintenance of the clinical benefits of pulse therapy, while preventing or attenuating these adverse effects, are warranted. Exercise training has the potential to counteract these adverse effects, but the efficacy and viability of this approach has yet to be explored. Hence, this randomized, controlled, parallel-group trial aims to investigate the effects of a home-based, supervised, 6-month exercise training program on a battery of musculoskeletal health parameters in women with systemic lupus erythematosus who recently underwent GC pulse therapy. Methods After baseline assessments, participants will be randomized to either the control or exercise group. Participants in both groups will receive usual care, while those randomized to the exercise group will also undergo a multimodal training program. Outcomes will be examined at baseline and after 3 and 6 months. Primary outcomes include bone mineral density by dual-energy x-ray absorptiometry, bone microarchitecture by high-resolution peripheral quantitative computed tomography, and circulating levels of bone turnover markers (β-CTX and PINP). Secondary outcomes include body composition, muscle strength and function, and aerobic capacity as well as feasibility and acceptability metrics. Conclusion The information gained from this investigation has the potential to inform care and management strategies for this and similarly affected patient groups.

Impact of Different Anti-Hyperglycaemic Treatments on Bone Turnover Markers and Bone Mineral Density in Type 2 Diabetes Mellitus Patients: A Systematic Review and Meta-Analysis.

Diabetic bone disease (DBD) is a frequent complication in patients with type 2 diabetes mellitus (T2DM), characterised by altered bone mineral density (BMD) and bone turnover marker (BTMs) levels. The impact of different anti-diabetic medications on the skeleton remains unclear, and studies have reported conflicting results; thus, the need for a comprehensive systematic review is of paramount importance. A systematic search was conducted in PubMed and the Cochrane Library. The primary outcomes assessed were changes in BMD in relation to different anatomical sites and BTMs, including mainly P1NP and CTX as well as OPG, OCN, B-ALP and RANK-L. Risk of bias was evaluated using the JADAD score. The meta-analysis of 19 randomised controlled trials comprising 4914 patients showed that anti-diabetic medications overall increased BMD at the lumbar spine (SMD: 0.93, 95% CI [0.13, 1.73], p = 0.02), femoral neck (SMD: 1.10, 95% CI [0.47, 1.74], p = 0.0007) and in total hip (SMD: 0.33, 95% CI [-0.25, 0.92], p = 0.27) in comparison with placebo, but when compared with metformin, the overall effect favoured metformin over other treatments (SMD: -0.23, 95% CI [-0.39, -0.07], p = 0.004). GLP-1 receptor agonists and insulin analogues seem to improve BMD compared to placebo, while SGLT2 inhibitors and thiazolidinediones (TZDs) showed no significant effect, although studies' number cannot lead to safe conclusions. For BTMs, TZDs significantly increased P1NP levels compared to placebo. However, no significant differences were observed for CTX, B-ALP, OCN, OPG, and RANK-L between anti-diabetic drugs and metformin or placebo. High heterogeneity and diverse follow-up durations among studies were evident, which obscures the validity of the results. This review highlights the variable effects of anti-diabetic drugs on DBD in T2DM patients, emphasising the need for long-term trials with robust designs to better understand these relationships and inform clinical decisions.

Association between bone turnover markers, bone mineral density, and serum osteoglycine in middle-aged men with Type 2 Diabetes mellitus

BackgroundPatients with Type 2 diabetes mellitus (T2DM) have decreased bone health. We aimed to investigate serum levels of bone turnover markers (BTMs) (markers of bone formation and bone resorption) and bone mineral density (BMD) at three sites (lumber, neck femur, and total femur) in middle-aged men with type 2 diabetes and to analyze the relationship between them. Also to evaluate serum osteoglycin as a novel marker and its relation to BTMs, BMD, and diabetic status.MethodsWe recruited seventy-eight patients with T2DM and thirteen non-diabetic, male volunteers as a control group. BMD was measured using a DEXA scan. BTMs (carboxy-terminal crosslinking telopeptide of type 1 collagen [CTX] and procollagen type 1 N propeptide [P1NP]), osteoglycin, PTH, and vitamin D were estimated. Data was compared among subjects and statistical analysis was performed.ResultsMost of the patients were having normal BMD with no significant difference between patients and the controls. BTMs and osteoglycin were significantly higher and vitamin D was significantly lower in the diabetic patients. Serum osteoglycin was positively correlated with DEXA Neck Femur (r = 0.233; p-value < 0.05).ConclusionBody mass index and Serum osteoglycin have a significant positive effect on BMD. Both markers of bone formation and bone resorption were increased indicating a state of increased bone turnover in T2DM.

Impact of medical therapy for hormone-secreting Pituitary tumors on bone.

Bone health is often impaired in patients with hormone-secreting pituitary tumors. Since medical therapy is central to their care, understanding how its use impacts on this is highly important. This review summarizes a systemmatic review of the literature on the effects of medical therapies for hormone-secreting pituitary tumors on bone. In acromegaly, medical therapy lowers bone turnover marker (BTM) levels, consistent with correction of the high bone turnover of active disease, and overall, areal bone mineral density (aBMD) does not change or increases. Somatostatin-receptor ligand (SRL) and pegvisomant-treated acromegaly patients have persistently reduced volumetric BMD and microarchitectural abnormalities of the peripheral skeleton, deficits that are similar to those in surgically-treated patients. Fracture risk remains elevated in medically-treated acromegaly patients but in conjunction with biochemical control the risk is lessened. Treatment of prolactin-secreting tumors with dopamine agonists is associated with improvements in aBMD, but this does not always fully normalize despite effective medical treatment of the prolactinoma. In one cross-sectional study, prolactinoma patients had lower total volumetric BMD and impaired microarchitecture suggesting that bone microstructure does not fully normalize despite dopamine agonist therapy. Cross-sectional studies show a high rate of VF in patients with prolactin-secreting tumors that is lowered on cabergoline therapy, but still the fracture rate of men and postmenopausal women is higher than that of controls in some studies. Studies on the effects of modern-day medical therapy for Cushing's disease on bone are lacking. More research is needed on the effectsof medical therapies for hormone secreting pituitary tumors on bone health.

Bone: A Neglected Endocrine Organ?

Bone has traditionally been viewed in the context of its structural contribution to the human body. Foremost providing necessary support for mobility, its roles in supporting calcium homeostasis and blood cell production are often afterthoughts. Recent research has further shed light on the ever-multifaceted role of bone and its importance not only for structure, but also as a complex endocrine organ producing hormones responsible for the autoregulation of bone metabolism. Osteocalcin is one of the most important substances produced in bone tissue. Osteocalcin in circulation increases insulin secretion and sensitivity, lowers blood glucose, and decreases visceral adipose tissue. In males, it has also been shown to enhance testosterone production by the testes. Neuropeptide Y is produced by various cell types including osteocytes and osteoblasts, and there is evidence suggesting that peripheral NPY is important for regulation of bone formation. Hormonal disorders are often associated with abnormal levels of bone turnover markers. These include commonly used bone formation markers (bone alkaline phosphatase, osteocalcin, and procollagen I N-propeptide) and commonly used resorption markers (serum C-telopeptides of type I collagen, urinary N-telopeptides of type I collagen, and tartrate-resistant acid phosphatase type 5b). Bone, however, is not exclusively comprised of osseous tissue. Bone marrow adipose tissue, an endocrine organ often compared to visceral adipose tissue, is found between trabecula in the bone cortex. It secretes a diverse range of hormones, lipid species, cytokines, and other factors to exert diverse local and systemic effects.

Changes in bone turnover markers 6–12 months after bariatric surgery

A rise in bone turnover markers (BTM) after bariatric surgery predicts poor bone health years later. This study explored factors associated with BTM and changes in BTM after bariatric surgery. Inclusion criteria were subjects 18 to 65 years of age with morbid obesity undergoing bariatric surgery. All data were measured before and 6 and 12 months after surgery. The study included 104 subjects: women/men: 83/21; mean age 43.1 (SD 8.4) years; BMI: 38.8 kg/m2 (SD 3.8). Surgery with Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) was performed in 84 (81%) and 20 (19%) subjects, respectively. From before to 6–12 months after surgery, procollagen type 1 N-terminal propeptid (P1NP) increased by 45.6 µg/L (95% CI 41.5–50.0, p < 0.001), and alkaline phosphatase (ALP) by 10 U/L (95% CI 7–14, p < 0.001). The increases were significantly larger after RYGB than after SG. The APOE- Ɛ3 allele was associated with low levels of BTM and high levels of leptin. There was an unfavourable increase in BTM after bariatric surgery. SG compared to RYGB and the presence of the APOE-Ɛ3 allele were associated with less unfavourable effects. The study emphasises the importance of optimal prophylactic interventions after bariatric surgery to prevent osteoporosis.

Skeletal effects of sleeve gastrectomy, by sex and menopausal status and in comparison to Roux-en-Y gastric bypass surgery.

Roux-en-Y gastric bypass (RYGB) has deleterious effects on bone mass, microarchitecture, and strength. Data are lacking on the skeletal effects of sleeve gastrectomy (SG), now the most commonly performed bariatric surgical procedure. We examined changes in bone turnover, areal and volumetric bone mineral density (aBMD, vBMD), and appendicular bone microarchitecture and estimated strength after SG. We compared the results to those previously reported after RYGB, hypothesizing lesser effects after SG than RYGB. Prospective observational cohort study of 54 adults with obesity undergoing SG at an academic center. Skeletal characterization with biochemical markers of bone turnover, dual-energy X-ray absorptiometry (DXA), quantitative computed tomography (QCT), and high-resolution peripheral QCT (HR-pQCT) was performed preoperatively and 6- and 12-months postoperatively. Over 12 months, mean percentage weight loss was 28.8%. Bone turnover marker levels increased, and total hip aBMD decreased -8.0% (95% CI -9.1%, -6.7%, p<0.01). Spinal aBMD and vBMD declines were larger in postmenopausal women than men. Tibial and radial trabecular and cortical microstructure worsened, as did tibial estimated strength, particularly in postmenopausal women. When compared to data from a RYGB cohort with identical design and measurements, some SG biochemical, vBMD, and radial microstructural parameters were smaller, while other changes were not. Bone mass, microstructure, and strength decrease after SG. Some skeletal parameters change less after SG than after RYGB, while for others, we find no evidence for smaller effects after SG. Postmenopausal women may be at highest risk of skeletal consequences after SG.

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 1 year. Patients' clinical data were collected. The levels of BTMs 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 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 decreased 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.

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.

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.

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.

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.