Biochemical Markers Of Bone Turnover Research Articles

Six months of voluntary alcohol consumption in male cynomolgus macaques reduces intracortical bone porosity without altering mineralization or mechanical properties

Chronic heavy alcohol consumption is a risk factor for low trauma bone fracture. Using a non-human primate model of voluntary alcohol consumption, we investigated the effects of 6 months of ethanol intake on cortical bone in cynomolgus macaques (Macaca fascicularis). Young adult (6.4 ± 0.1 years old, mean ± SE) male cynomolgus macaques (n = 17) were subjected to a 4-month graded ethanol induction period, followed by voluntary self-administration of water or ethanol (4 % w/v) for 22 h/d, 7 d/wk. for 6 months. Control animals (n = 6) consumed an isocaloric maltose-dextrin solution. Tibial response was evaluated using densitometry, microcomputed tomography, histomorphometry, biomechanical testing, and Raman spectroscopy. Global bone response was evaluated using biochemical markers of bone turnover. Monkeys in the ethanol group consumed an average of 2.3 ± 0.2 g/kg/d ethanol resulting in a blood ethanol concentration of 90 ± 12 mg/dl in longitudinal samples taken 7 h after the daily session began. Ethanol consumption had no effect on tibia length, mass, density, mechanical properties, or mineralization (p > 0.642). However, compared to controls, ethanol intake resulted in a dose-dependent reduction in intracortical bone porosity (Spearman rank correlation = −0.770; p < 0.0001) and compared to baseline, a strong tendency (p = 0.058) for lower plasma CTX, a biochemical marker of global bone resorption. These findings are important because suppressed cortical bone remodeling can result in a decrease in bone quality. In conclusion, intracortical bone porosity was reduced to subnormal values 6 months following initiation of voluntary ethanol consumption but other measures of tibia architecture, mineralization, or mechanics were not altered.

Albumin-to-alkaline phosphatase ratio may be a better predictor of survival than sclerostin, dickkopf-1, osteopontin, osteoprotegerin and osteocalcin

ObjectivesThe value of biochemical markers of bone turnover (BTMs) in predicting survival and disease remains unclear. In a prospective study we evaluated the novel biomarkers for bone turnover sclerostin, dickkopf-1 (DKK-1), osteopontin (OPN), osteoprotegerin (OPG) and osteocalcin (OC), as well as a traditional biomarker, alkaline phosphatase (ALP) in relation to risk of mortality, cardiovascular events and fractures. Participantsand Methods:Routine blood tests and serum BTMs, including ALP, were analyzed in patients with hip fracture n = 97, stroke n = 71 and healthy volunteers n = 83 (mean age 86, 83 and 77, respectively), followed for 7 years. Hazard Ratios (HR) were calculated for mortality, cardiovascular events and fractures in relation to these biomarkers. After adding the albumin-to-ALP ratio (AAPR) a post hoc analysis was performed. Results120 participants died during the study. In the entire group of patients and volunteers (n = 251) higher AAPR (HR 0.28, 95 % CI 0.14–0.59, p < 0.001) was associated with decreased mortality. OPN and OPG were associated with mortality risk only in the univariate statistical analysis. HR for high AAPR in relation to new cardiovascular events was borderline significant (HR 0.29, 95 % CI 0.08–1.06, p = 0.061). None of the examined biomarkers were associated with new fractures, nor with an increased risk of a new cardiovascular event. ConclusionsAAPR may be a better predictor of mortality than the more novel BTMs, and higher AAPR could be associated with longer life expectancy. Further studies should determine the clinical usefulness of AAPR as a biomarker of mortality and cardiovascular disease.

Research progress of periostin and osteoporosis.

Periostin, as a unique extracellular matrix, is mainly produced during ontogeny and in adult connective tissues that bear mechanical loads, such as heart valves, skin, periodontal ligaments, tendons, and bones. By binding to the integrin on the cell surface and activating Wnt/β-catenin, NF-κB, Fak and other signaling pathways, it regulates the tissues in vivo positively or negatively, and also has different effects on the occurrence and development of various diseases. Periostin is an important factor, which can promote cell proliferation, stimulate tissue repair and maintain the integrity of the structure and function of connective tissue. It also promotes the formation, regeneration and repairation of bone. Recent studies have shown that periostin is important in bone metabolic diseases. The increased expression of periostin can affect bone mineral density at different sites, and its relationship with traditional biochemical markers of bone turnover has not been conclusively established. This article reviews the research results and potential applications of periostin in osteoporosis.

Assessment of Biochemical Bone Turnover Markers in Polish Healthy Children and Adolescents.

Assessing bone turnover in paediatric populations is crucial for understanding the physiological changes occurring during skeletal development and identifying potential abnormalities. The objective of this study was to assess osteocalcin (OC), bone alkaline phosphatase (BALP), and C-terminal telopeptide of type I collagen (CTX-I) levels reflecting bone formation and resorption for age and sex in Polish healthy children and adolescents. A total of 355 healthy normal-weight children and adolescents (46.5% girls) aged 1-18 years old were recruited. Total body less head (TBLH) and spine L1-L4 were used in children to assess bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA). Bone marker concentrations were determined by immunoenzymatic methods. Bone marker levels in girls and boys started with higher values in the first year of life and subsequently decreased until reaching a nadir during the prepubertal period. The pubertal peak values of bone markers were reached at 11-13 years old in boys and at 9-11 years old in girls. After puberty, the adolescents showed a gradual decline in bone marker concentrations to the values observed in adults. We found positive correlations between OC level and TBLH-BMD (r = 0.329, p = 0.002), TBLH-BMD Z-score (r = 0.245, p = 0.023), and L1-L4 BMD (r = 0.280, p = 0.009) in the prepubertal group. We showed serum levels of bone turnover markers-BALP, OC, and CTX-I-in relation to age and sex in healthy Polish children and adolescents. The age intervals of these markers for girls and boys aged 1-18 years old may be clinically useful in the assessment of bone metabolism in individuals with skeletal disorders.

Gut microbial community and fecal metabolomic signatures in different types of osteoporosis animal models.

The gut microbiota (GM) constitutes a critical factor in the maintenance of physiological homeostasis. Numerous studies have empirically demonstrated that the GM is closely associated with the onset and progression of osteoporosis (OP). Nevertheless, the characteristics of the GM and its metabolites related to different forms of OP are poorly understood. In the present study, we examined the changes in the GM and its metabolites associated with various types of OP as well as the correlations among them. We simultaneously established rat postmenopausal, disuse-induced, and glucocorticoid-induced OP models. We used micro-CT and histological analyses to observe bone microstructure, three-point bending tests to measure bone strength, and enzyme-linked immunosorbent assay (ELISA) to evaluate the biochemical markers of bone turnover in the three rat OP models and the control. We applied 16s rDNA to analyze GM abundance and employed untargeted metabolomics to identify fecal metabolites in all four treatment groups. We implemented multi-omics methods to explore the relationships among OP, the GM, and its metabolites. The 16S rDNA sequencing revealed that both the abundance and alterations of the GM significantly differed among the OP groups. In the postmenopausal OP model, the bacterial genera g__Bacteroidetes_unclassified, g__Firmicutes_unclassified, and g__Eggerthella had changed. In the disuse-induced and glucocorticoid-induced OP models, g__Akkermansia and g__Rothia changed, respectively. Untargeted metabolomics disclosed that the GM-derived metabolites significantly differed among the OP types. However, a Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that it was mainly metabolites implicated in lipid and amino acid metabolism that were altered in all cases. An association analysis indicated that the histidine metabolism intermediate 4-(β-acetylaminoethyl) imidazole was common to all OP forms and was strongly correlated with all bone metabolism-related bacterial genera. Hence, 4-(β-acetylaminoethyl) imidazole might play a vital role in OP onset and progression. The present work revealed the alterations in the GM and its metabolites that are associated with OP. It also disclosed the changes in the GM that are characteristic of each type of OP. Future research should endeavor to determine the causal and regulatory effects of the GM and the metabolites typical of each form of OP.

Pre-treatment bone turnover does not influence the level of the response to alendronate in postmenopausal osteoporosis at the bone tissue level.

The main effect of anti-resorptive agents such as bisphosphonates is a reduction of bone resorption, with a consequent marked decrease of bone turnover. This post-hoc analysis investigated the changes of histomorphometric parameters of bone turnover after alendronate (ALN), according to the baseline turnover. Ninety postmenopausal women underwent a transiliac bone biopsy before and after 6 (n = 44) or 12 (n = 46) months of treatment with ALN (70 mg/week). The dynamic parameters reflecting the bone formation and bone turnover were mineralizing surface (MS/BS; %), bone formation rate (BFR/BS; μm3/μm2/d), and activation frequency (Ac.f; /yr). Biochemical markers sPINP and the sCTX were assessed before treatment and after 3, 6, and 12 months. Subjects were divided into quartiles based on the baseline values of BFR/BS. At baseline, MS/BS and Ac.f were significantly different (p < 0.0001) among the BFR quartiles. sCTX and sP1NP were not significantly different among quartiles. After ALN treatment, MS/BS was not significantly different among quartiles but Ac.f remained significantly lower in the first quartile compared to the third and fourth ones (p < 0.03). The absolute value of the difference between pre- and post-treatment significantly correlated with the baseline BFR/BS but when expressed in percent of the baseline value, the magnitude of the diminutions of MS/BS, Ac.f, sCTX, and sP1NP was similar in the four baseline BFR quartiles. The percentage response to ALN appeared independent of the baseline level of bone turnover. After treatment, the bone turnover tended to be similar in all BFR quartiles. This analysis investigated the influence of baseline turnover measured by bone histomorphometry on the effect of alendronate. When expressed in percent of pre-treatment values, the decreases of histomorphometric parameters and biochemical markers of bone turnover were independent of the baseline turnover.

Randomised trial of genetic testing and targeted intervention to prevent the development and progression of Paget’s disease of bone

IntroductionPaget’s disease of bone (PDB) frequently presents at an advanced stage with irreversible skeletal damage. Clinical outcomes might be improved by earlier diagnosis and prophylactic treatment.MethodsWe randomised 222 individuals at...

Cistanche deserticola improves ovariectomized-induced osteoporosis mainly by regulating lipid metabolism: Insights from serum metabolomics using UPLC/Q-TOF-MS

Ethnopharmacological relevanceCistanche deserticola (C. deserticola) is an edible and traditional medicine widely used in China, which has been confirmed to be effective in the treatment of postmenopausal osteoporosis (PMOP). Despite its proven efficacy, the exact role of C. deserticola in bone metabolism and its underlying mechanism has remained unclear. Aim of the studyIn this research, we employed an in vivo model utilizing ovariectomized (OVX) rats to characterize the anti-osteoporotic activity and metabolic mechanism of the ethanol extract of C. deserticola (CHE). Materials and methodsFifty female Sprague-Dawley (SD) rats were randomly divided into five groups including sham operation group, model group, 0.1 g/kg estradiol valerate (EV) group as the positive control, low (0.6 g/kg) and high (1.2 g/kg) dosage CHE groups. Biochemical parameter analyses and histopathological experiments were conducted to assess the pharmacodynamic effects. Metabolomic analysis was conducted on serum samples to examine the metabolic profiles, identify potential biomarkers, and elucidate the metabolic pathways associated with CHE in OVX rats. ResultsCHE treatment demonstrated significant anti-osteoporosis activity by regulating serum biochemical markers of bone turnover, improving cancellous bone structure, and reversing the decrease in bone mineral density. Furthermore, the clinical equivalent dose group (CHL) achieved superior overall outcomes. The main interventions of CHE on OVX rats involved the modulation of several key pathways, including steroid hormone biosynthesis, arachidonic acid metabolism, tyrosine and tryptophan metabolism, biotin metabolism, regulation of TRP channels by inflammatory mediators, primary bile acid biosynthesis, regulation of lipolysis in adipocytes, and bile secretion. 23 potential efficacy-related biomarkers within the metabolic network were identified. Among them, long-chain unsaturated fatty acids (eg. DHA and docosapentaenoic acid), steroid hormones, amino acids and carbohydrates were strongly correlated with bone resorption and formation markers. Additionally, it was observed four pathways (nucleotide, carbon, amino acid, and lipid metabolism) were implicated in the effects of CHE. ConclusionThis study demonstrates that CHE improves bone loss in PMOP mainly through regulating lipid metabolism pathways, which provides an evidence base for CHE treatment of PMOP.

Effect of Anamorelin, a Ghrelin Receptor Agonist, on Muscle and Bone in Adults With Osteosarcopenia.

Anamorelin, a ghrelin receptor agonist known to stimulate the pulsatile release of GH from the pituitary, has the potential to improve musculoskeletal health in adults with osteosarcopenia. To determine the effect of anamorelin treatment for 1 year on muscle mass and strength and on biochemical markers of bone turnover in adults with osteosarcopenia (OS). Randomized, placebo-controlled, 1-year anamorelin intervention trial. The Bone Metabolism Laboratory at the USDA Nutrition Center at Tufts University. 26 men and women, age 50 years and older, with OS. Muscle mass by D3-creatine dilution and lean body mass (LBM) and bone mineral density (BMD) by dual-energy X-ray absorptiometry, muscle strength, serum IGF-1, and bone turnover markers, serum procollagen 1 intact N-terminal (P1NP), and C-terminal telopeptide (CTX). Anamorelin did not have a significant effect on muscle mass or LBM; it significantly increased knee flexion torque at 240°/s by 20% (P = .013) and had a similar nonstatistically significant effect on change in knee extension; it increased bone formation (P1NP) by 75% (P = .006) and had no significant effect on bone resorption (CTX) or BMD. Serum IGF-1 increased by 50% in the anamorelin group and did not change in the placebo group (P = .0001 for group difference). In this pilot study, anamorelin did not significantly alter muscle mass; however, it may potentially improve lower extremity strength and bone formation in addition to increasing circulating IGF-1 levels in adults with OS. Further study of anamorelin in this population is warranted.

Osteoporosis: Investigations and Monitoring.

Osteoporosis is characterized by microarchitectural disruption of the bone, decrease in bone mineral density, and increased skeletal fragility and risk of fracture. Osteoporosis occurs due to the decoupling of bone formation and bone resorption, with a significant increase in resorption. This review article focuses on the role of laboratory investigations in the diagnosis and monitoring of treatment in patients with osteoporosis. This review article collected literature from various databases using keywords such as 'Laboratory investigations', 'Osteoporosis', 'Diagnosis', 'Monitoring', and 'Bone turnover markers'. Laboratory investigations, including serum calcium, alkaline phosphatase, vitamin D, and parathormone, are commonly performed tests to exclude secondary causes of osteoporosis and monitor the response to therapy. The biochemical markers of bone turnover are newly emerged tests for monitoring individual patients with osteoporosis. These markers are classified as bone formation and resorption markers, measurable in both serum and urine. The use of these markers is limited by biological and analytical variability. The International Federation of Clinical Chemistry and Laboratory Medicine and the International Osteoporosis Foundation recommend serum procollagen type 1 amino-terminal propeptide as the bone formation marker and β-form of C-terminal cross-linked telopeptide of type I collagen (β-CTx-1/β-CrossLaps) as the marker of choice, using standardized procedures. However, in specific cases, such as patients with chronic renal disease, CTx-1 is replaced by the resorption marker tartrate-resistant acid phosphatase 5b, as its levels are not affected by renal excretion. Bone turnover markers have emerged as tools for the assessment of osteoporosis, using standardized procedures, and are useful in monitoring therapy and treatment compliance.

Osteoporosis: Molecular Pathology, Diagnostics, and Therapeutics.

Osteoporosis is a major public health concern affecting millions of people worldwide and resulting in significant economic costs. The condition is characterized by changes in bone homeostasis, which lead to reduced bone mass, impaired bone quality, and an increased risk of fractures. The pathophysiology of osteoporosis is complex and multifactorial, involving imbalances in hormones, cytokines, and growth factors. Understanding the cellular and molecular mechanisms underlying osteoporosis is essential for appropriate diagnosis and management of the condition. This paper provides a comprehensive review of the normal cellular and molecular mechanisms of bone homeostasis, followed by an in-depth discussion of the proposed pathophysiology of osteoporosis through the osteoimmunological, gut microbiome, and cellular senescence models. Furthermore, the diagnostic tools used to assess osteoporosis, including bone mineral density measurements, biochemical markers of bone turnover, and diagnostic imaging modalities, are also discussed. Finally, both the current pharmacological and non-pharmacological treatment algorithms and management options for osteoporosis, including an exploration of the management of osteoporotic fragility fractures, are highlighted. This review reveals the need for further research to fully elucidate the molecular mechanisms underlying the condition and to develop more effective therapeutic strategies.

Alloferon-1 ameliorates estrogen deficiency-induced osteoporosis through dampening the NLRP3/caspase-1/IL-1β/IL-18 signaling pathway

Alloferon-1 is an insect polypeptide that has anti-inflammatory, antitumor and antiviral activity. This study aimed to determine the effects of alloferon-1 on estrogen deficiency-induced osteoporosis and explore the associated mechanism using a murine model of ovariectomy (OVX)-induced osteoporosis. Results showed that alloferon-1 prevented ovariectomy‑induced body weight gain, bone loss and bone mineral content reduction, affected biochemical markers of bone turnover, and restored the microstructure of bone trabeculae. Moreover, alloferon-1 suppressed the expression of the ovariectomy‑mediated inflammatory cytokines in the vertebrae bone tissues, including nucleotide-binding oligomerization domain-like-receptor family pyrin domain-containing 3 (NLRP3), cysteinyl aspartate specific proteinase-1 (Caspase-1), interleukin 1β (IL-1β) and interleukin 18 (IL-18) which were determined by immunofluorescence staining and western blot. Overall, the present study provides evidence for the effectiveness of alloferon-1 against estrogen deficiency-induced osteoporosis, suggesting an alternative drug or an auxiliary modulator for the treatment of postmenopausal osteoporosis (PMOP).

Cinacalcet in patients with primary hyperparathyroidism; a review

Primary hyperparathyroidism (PHPT) is a condition characterized by the parathyroid glands’ overproduction of parathyroid hormone (PTH). These increases calcium levels in the blood, leading to various symptoms and complications. Cinacalcet is a promising therapeutic option for patients with PHPT who are unable or unwilling to undergo surgery. It effectively reduces serum calcium and PTH levels, improving biochemical markers of bone turnover and renal function. However, more research is needed to determine the optimal dosage, duration, and long-term effects of cinacalcet treatment in this patient population. Clinicians should carefully consider the risks and benefits of cinacalcet therapy individually and involve patients in shared decision-making.

Efficacy of switching from teriparatide to zoledronic acid or denosumab on bone mineral density and biochemical markers of bone turnover in older patients with severe osteoporosis: a real-life study.

Osteoporosis is characterized by loss of bone mass and susceptibility to fracture. Skeletal effects of teriparatide (TPT) are not persistent after drug withdrawal and sequential therapy with bisphosphonates or denosumab (Dmab) after TPT discontinuation represents a valid option. Here, the two sequential strategies were evaluated in severe osteoporotic patients. The study retrospectively enrolled 56 severe osteoporotic patients who received TPT for 24 months followed by 24 months of zoledronic acid (ZOL) (TPT + ZOL) or Dmab (TPT+Dmab). Clinical features, incident fractures, bone mineral density (BMD) measurements, and bone marker profiles were collected. One-way ANOVA analyzed the difference between mean T-scores at baseline, after 24 months of TPT, and after 2 doses of ZOL or after at least 3 doses of Dmab. Twenty-three patients received TPT + ZOL (19 females, 4 males; median [IR] age, 74.3 [66.9, 78.6] years) and 33 patients received TPT+Dmab (31 females, 2 males; mean [IR] age, 66.6 ± 11.3 years). Mean lumbar and hip T-scores were increased after both TPT + ZOL and TPT+Dmab (all p < 0.05 vs baseline). The size effects induced by TPT + ZOL on the lumbar and hip BMD T-scores were similar to those observed with TPT+Dmab with mean T-scores increases of about 1 and 0.4 SD, respectively. No significant between-group differences were identified. Incident fragility fractures occurred in 3 (13%) patients treated with TPT + ZOL and in 5 (15%) patients treated with TPT+Dmab. Sequential TPT + ZOL therapy is likely to increase bone mineralization at the lumbar level and to stabilize it at the femoral level, similarly to what obtained with the sequential TPT+Dmab. Both ZOL and Dmab are suggested to be effective sequential treatments after TPT.

Ameliorative effects of Kyung-Ok-Ko and its mixture with Pueraria lobata Ohwi on postmenopausal osteoporosis by promoting phytoestrogenic activity in rats.

Kyung-Ok-Ko (KOK) is a popular traditional medicine used as a natural alternative to hormone replacement therapy for treating postmenopausal symptoms in Asia. Pueraria lobata Ohwi (P. lobata) is rich in isoflavones and has been traditionally used in combination with other herbs to produce synergistic and pharmaceutical effects via a multi-target approach for disease treatment. We aimed to investigate the phytoestrogenic effects of KOK extract against postmenopausal symptoms in ovariectomized (OVX) rats and confirm its efficacy by mixing KOK and P. lobata extracts. OVX rats were daily oral administrated with KOK and KOK + P. lobata mixture extracts (300-400 mg/kg) and their body weight and tail temperature were monitored for 12 weeks. The biochemical parameters, estradiol levels, and bone turnover markers were measured in the serum samples. Moreover, the estrogen receptor, ER-α and ER-β expression in the uterus and the uterus morphology were evaluated. AMPK, ATG1/ULK1, and mTOR protein expression in the liver were assessed. The 12-week treatment with KOK and KOK + P. lobata mixture extracts did not cause liver damage or hormonal changes in the OVX rats. The treatments reduced the high lipid accumulation-related body weight gain and the tail temperature increase that was induced by ovariectomy. Further, it exhibited protective effects against hyperlipidemia and osteoporosis. No significant difference was observed in uterine weight compared to the OVX-treated group, while endometrial thickness reduction inhibition was observed due to ovariectomy. Bone mineral density (BMD) and serum osteocalcin levels, which decreased in OVX rats, increased with both treatments. Western blotting analysis showed that ER-α and ER-β were not expressed in the treated rats, whereas these proteins were expressed in Sham-operated rats. No significant differences in the phosphorylation of AMPK were observed; however, the ATG1/ULK1 and mTOR protein phosphorylation levels were upregulated and downregulated in the treated rats compared to those of OVX rats, respectively. This is the first in vivo study observing the efficacy and synergistic effects of the mixture of KOK and P. lobata. Our results suggest the potential of KOK and KOK + P. lobata mixture as an alternative therapy for alleviating menopausal symptoms.

Comparison of bone microstructure and strength in the distal radius and tibia between the different types of primary hypertrophic osteoarthropathy: an HR-pQCT study

SummaryPrimary hypertrophic osteoarthropathy (PHO) is a hereditary bone disease that is grouped into PHO autosomal recessive 1 (PHOAR1) and PHO autosomal recessive 2 (PHOAR2) due to different causative genes. Data comparing bone microstructure between the two subtypes are scarce. This is the first study to find that PHOAR1 patients had inferior bone microstructure compared with PHOAR2 patients.PurposeThe primary goal of this study was to assess bone microarchitecture and strength in PHOAR1 and PHOAR2 patients and to compare them with age- and sex-matched healthy controls (HCs). The secondary goal was to assess the differences between PHOAR1 and PHOAR2 patients.MethodsTwenty-seven male Chinese PHO patients (PHOAR1 = 7; PHOAR2 = 20) were recruited from Peking Union Medical College Hospital. The areal bone mineral density (aBMD) was assessed by dual-energy X-ray absorptiometry (DXA). Peripheral bone microarchitecture at the distal radius and tibia were evaluated by high-resolution peripheral quantitative computed tomography (HR-pQCT). Biochemical markers of PGE2, bone turnover, and Dickkopf-1 (DKK1) were investigated.ResultsCompared with HCs, PHOAR1 and PHOAR2 patients had distinctively larger bone geometry, substantially lower vBMD at the radius and tibia, and compromised cortical microstructure at the radius. For trabecular bone, PHOAR1 and PHOAR2 patients showed different changes at the tibia. PHOAR1 patients had significant deficits in the trabecular compartment, resulting in lower estimated bone strength. Conversely, PHOAR2 patients showed a higher trabecular number, narrower trabecular separation, and lower trabecular network inhomogeneity than HCs, translating into preserved or slightly high estimated bone strength.ConclusionPHOAR1 patients had inferior bone microstructure and strength compared with PHOAR2 patients and HCs. Additionally, this study was the first to find differences in the bone microstructure between PHOAR1 and PHOAR2 patients.

The Relationship Between Stress Fractures and Bone Turnover Markers Is Unclear in Athletic and Military Populations: A Critically Appraised Topic

Clinical Scenario: Having an indication of how bone is remodeling in response to training load could help identify athletes and military personnel at increased stress fracture (SFx) risk. Direct assessment of bone remodeling is impractical. Biochemical markers of bone turnover are used as an indirect measure of bone remodeling and have potential to inform prevention and treatment efforts. To date, the relationship between bone turnover markers and SFxs in athletes or military personnel remains unclear. Clinical Question: Are SFxs related to bone turnover markers in athletes and military personnel? Summary of Key Findings: Seven met eligibility criteria. In five studies, an association between SFxs and bone turnover markers existed. Clinical Bottom Line: The evidence supporting a relationship between SFxs and bone turnover markers in athletes and military personnel is mixed. While five of the seven studies reported some type of relationship, no studies prospectively measured bone turnover markers in a group of athletes or military personnel without an SFx or without SFx history and followed them over time to reassess bone turnover markers upon SFx occurrence. Strength of Clinical Recommendation: In accordance with the Strength of Recommendation Taxonomy, Grade C is the most appropriate strength of recommendation rating.

Bone status and HCV infection in thalassemia major patients.

Hepatitis C virus (HCV) infection increases the risk for osteoporosis but this relationship has not been investigated among multi-transfused patients with thalassemia major (TM). We cross-sectionally explored the association of HCV infection with bone mineral density (BMD), vitamin D, and bone turnover biomarkers in TM. We considered 130 TM patients (41.89±5.49years, 67 females) enrolled in the E-MIOT (Extension-Myocardial Iron Overload in Thalassemia) Network. BMD measurements taken at the lumbar spine, femoral neck and total hip were expressed as Z-scores, with a BMD Z-score≤-2.0 indicating low bone mass. Z-scores were not associated with gender, iron overload indices, vitamin D levels, and biochemical bone turnover markers, but decreased with aging and in presence of hypogonadism and were directly correlated with body mass index (BMI). The prevalence of low bone mass was 70.7%. Three groups of patients were identified: 78 who never contracted the infection (group 0), 72 who cleared HCV (group 1), and 29 with chronic HCV infection (CHC) (group 2). All Z-scores progressively decreased according to HCV status from group 0 to group 2. Osteocalcin levels were significantly lower in groups 2 and 1 than in group 0. CHC patients were more likely to have low bone mass compared to HCV naive patients, after adjusting for age, BMI, hypogonadism, and pancreatic iron. In TM, CHC appears as one additive risk factor for low bone mass and osteocalcin may play a role in this association.

Vitamin D and Calcium in Osteoporosis, and the Role of Bone Turnover Markers: A Narrative Review of Recent Data from RCTs

Osteoporosis is a common disease, defined primarily by a low measured bone density, which is associated with an increased risk of fragility fractures. Low calcium intake and vitamin D deficiency seem to be positively correlated with the prevalence of osteoporosis. Although they are not suitable for the diagnosis of osteoporosis, the biochemical markers of bone turnover can be measured in serum and/or urine, enabling the assessment of the dynamic bone activity and the short-term effectiveness of the osteoporosis treatment. Calcium and vitamin D are essential for maintaining bone health. The aim of this narrative review is to summarize the effects of vitamin D and calcium supplementation separately and in combination, on bone density and circulating serum and blood plasma vitamin D, calcium, parathyroid hormone levels, markers of bone metabolism concentrations, and clinical outcomes, such as falls and osteoporotic fractures. We searched the PubMed online database to find clinical trials from the last five years (2016-April 2022). A total of 26 randomized clinical trials (RCTs) were included in this review. The present reviewed evidence suggests that vitamin D alone or in combination with calcium increases circulating 25(OH)D. Calcium with concomitant vitamin D supplementation, but not vitamin D alone, leads to an increase in BMD. In addition, most studies did not detect significant changes in circulating levels of plasma bone metabolism markers, nor in the incidence of falls. Instead, there was a decrease in blood serum PTH levels in the groups receiving vitamin D and/or Ca supplementation. The plasma vitamin D levels at the beginning of the intervention, and the dosing regimen followed, may play a role in the observed parameters. However, further study is needed to determine an appropriate dosing regimen for the treatment of osteoporosis and the role of bone metabolism markers.

Gut microbiota and fecal metabolic signatures in rat models of disuse-induced osteoporosis.

Assessing the correlation between gut microbiota (GM) and bone homeostasis has increasingly attracted research interest. Meanwhile, GM dysbiosis has been found to be associated with abnormal bone metabolism. However, the function of GM in disuse-induced osteoporosis (DIO) remains poorly understood. In our research, we evaluated the characteristics of GM and fecal metabolomics to explore their potential correlations with DIO pathogenesis. DIO rat models and controls (CON) underwent micro-CT, histological analyses, and three-point bending tests; subsequently, bone microstructures and strength were observed. ELISAs were applied for the measurement of the biochemical markers of bone turnover while GM abundance was observed using 16S rDNA sequencing. Metabolomic analyses were used to analyze alterations fecal metabolites. The potential correlations between GM, metabolites, and bone loss were then assessed. In the DIO group, the abundance of GM was significantly altered compared to that in the CON group. Moreover, DIO significantly altered fecal metabolites. More specifically, an abnormally active pathway associated with bile acid metabolism, as well as differential bacterial genera related to bone/tissue volume (BV/TV), were identified. Lithocholic acid, which is the main secondary bile acid produced by intestinal bacteria, was then found to have a relationship with multiple differential bacterial genera. Alterations in the intestinal flora and metabolites in feces, therefore, may be responsible for DIO-induced bone loss. The results indicated that changes in the abundance of GM abundance and fecal metabolites were correlated with DIO-induced bone loss, which might provide new insights into the DIO pathogenesis. The detailed regulatory role of GM and metabolites in DIO-induced bone loss needs to be explored further.