Bone Formation Markers Research Articles

Tibial Insufficiency Fracture with Characteristics of an Atypical Fracture: A Rare Case and Literature Review

Background and Objectives: Osteoporosis is becoming more prevalent with the rise in the aging population, leading to the increased use of bisphosphonates for treatment. While these medications are effective in preventing osteoporotic fractures, long-term use has been associated with atypical insufficiency fractures, primarily in the femur. However, atypical fractures in other weight-bearing bones, such as the tibia, have rarely been reported. This study aims to present a case of an atypical insufficiency fracture of the tibia in an elderly female who has been on long-term bisphosphonate therapy and to review treatment outcomes within the context of the current literature. Patient concerns: A 76-year-old female presented with pain in the proximal right tibia, developing two months prior without trauma. She had been receiving long-term bisphosphonate therapy for osteoporosis, initially taking sodium risedronate orally for 4 years, followed by intravenous ibandronate for 10 years. Physical examination revealed localized tenderness, and radiographs showed cortical thickening and a horizontal fracture line in the proximal right tibia. MRI confirmed these findings, along with surrounding edema. The laboratory results were mostly normal, but the bone formation marker osteocalcin was significantly reduced. The patient had a history of insufficiency fractures in the ipsilateral tibia and contralateral femur, previously treated conservatively with teriparatide. A similar conservative approach was attempted but failed, leading to surgical intervention with intramedullary nailing and supplementary plating. At the 8-month follow-up, the patient showed successful fracture union and resolution of symptoms. Conclusion: Long-term use of bisphosphonates, though effective for osteoporosis, can lead to atypical insufficiency fractures, primarily in the femur but also occasionally in the tibia. Clinicians should consider this possibility when patients present with pain in weight-bearing bones without a history of trauma. Prompt diagnosis through thorough history-taking, physical examination, and appropriate imaging is essential to ensure timely management.

Bone Mineral Density, Bone Biomarkers, and Joints in Acute, Post, and Long COVID-19: A Systematic Review

SARS-CoV-2 is highly transmissible and affects the respiratory system. People with COVID-19 are at higher risk of physical and mental health conditions, which could impact bone health. The aim of this review was to explore the effects of COVID-19 on BMD, BTMs, and joints. An electronic search of the PubMed, Web of Science, Scopus, and Ovid Medline databases considered studies published between 1 January 2020 and 1 November 2023. The search was limited to English, original studies in adult humans. The title and abstract of the identified papers were screened, followed by a full-text review using inclusion and exclusion criteria. The data extracted included the study and participant characteristics, BTMs, BMD, and joint abnormalities. The Newcastle–Ottawa scale quality assessment tool was used to assess the risk of bias. Five studies involving 305 out of 495 infected individuals observed a reduced BMD after COVID-19, with the most significant reduction occurring a year later. Both bone resorption and bone formation markers decreased, while regulatory markers showed higher levels in infected patients. COVID-19 may harm bone health by increasing bone regulatory markers and reducing bone formation and absorption, leading to a lower BMD. Elderly, frail, and osteopenic or osteoporotic individuals are at higher risk and should be regularly monitored for bone loss if they have long COVID.

Association of bone turnover markers and craving reduction in patients with alcohol use disorder during withdrawal: Exploring the role of bone-brain axis.

Alcohol use disorder (AUD) is associated with imbalanced bone turnover and psychological symptoms, but the relationship between bone and brain remains unclear. The study analyzed serum levels of a bone formation marker, procollagen type 1 N-terminal propeptide (P1NP), and bone resorption marker, C-terminal telopeptide of type I collagen (CTX-1), in AUD patients before and after 2 weeks of alcohol withdrawal and investigated their correlation with psychological symptoms. Ninety patients with AUD and 117 healthy controls were recruited. P1NP and CTX-1 levels were measured using Enzyme-Linked Immunosorbent Assay. The Penn Alcohol Craving Scale (PACS), Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI) were assessed in the AUD group at baseline, week 1, and week 2 of withdrawal. Baseline CTX-1 levels, along with the CTX-1/P1NP and P1NP/CTX-1 ratio, were higher in the AUD group than controls. Over the 2-week withdrawal, PACS, BDI, and BAI scores demonstrated significant reductions. P1NP (p < 0.001) and P1NP/CTX-1 ratio increased (p < 0.001), while CTX-1/P1NP ratio decreased (p < 0.001), indicating a propensity toward bone formation. Univariate analysis revealed that reductions in PACS, BDI, and BAI scores during withdrawal correlated with increased P1NP levels and decreased CTX-1/P1NP ratios. However, multivariate analysis indicated that only PACS score reductions correlated with these changes. Bone metabolism shifted toward increased bone formation and decreased bone resorption during 2-week alcohol withdrawal. The correlation between improvements in bone turnover markers and reduction in craving scores during withdrawal supports the concept of the bone-brain axis.

Perturbation Patterns of Bone Metabolism Secondary to COVID-19 Among Nigerian Healthcare Workers

&amp;lt;i&amp;gt;Background&amp;lt;/i&amp;gt;: Severe acute respiratory coronavirus-2 (SARS-CoV-2), the etiologic agent of coronavirus disease of 2019 (COVID-19) is known to affect several organ systems. However, the disease’s influence on bone metabolism is poorly characterized especially among native Nigerians. Consequently, the current study explored the effect of the disease on bone metabolism among Nigerian healthcare workers (HCWs). &amp;lt;i&amp;gt;Methods:&amp;lt;/i&amp;gt; This was a prospective longitudinal study conducted in the Department of Chemical Pathology of the Rivers State University Teaching Hospital among unvaccinated HCWs in Rivers State, Southern Nigeria. Eligible HCWs (n=96) were followed up from when they unwittingly had contact with SARS-CoV-2 infected/COVID-19 patients until they developed symptomatic RT-PCR-confirmed COVID-19. Demographic, anthropometric, clinical, and laboratory data were obtained before and at diagnosis/confirmation of COVID-19 among the eligible HCWs. Statistical analysis was done using descriptive/inferential statistics at a p-value of &amp;lt;0.05. &amp;lt;i&amp;gt;Results&amp;lt;/i&amp;gt;: At COVID-19 diagnosis, the HCWs had increased levels of inflammatory markers (procalcitonin, C-reactive protein, and D-dimer), raised bone resorption marker (s-CTX), but reduced bone formation marker (s-PINP) compared to the pre-COVID-19 parameters (p&amp;lt;0.001). These cardinal biochemical findings were more prominent among those with severe disease variant than those with non-severe disease variant (p&amp;lt;0.001). In addition, a negative correlation pattern was observed between these inflammatory markers and the bone formation marker, however, a positive correlation was observed between the inflammatory markers and the bone resorption marker (p&amp;lt;0.001). &amp;lt;i&amp;gt;Conclusion: &amp;lt;/i&amp;gt;The current finding indicates perturbation of bone metabolism, associated with increased bone resorption pattern, secondary to COVID-19 among the studied population. Hence, it is highly recommended that the evaluation of bone metabolism status be incorporated into the management protocols for COVID-19.

Protective effects of electroacupuncture on senile osteoporosis in rats.

The objectives were to explore the protective effects of electroacupuncture (EA) on senile osteoporosis in aged rats and investigate the underlying mechanisms. This study included aged (24-month-old; n = 16) and young (3-month-old; n = 8) male Sprague-Dawley rats. Aged rats were further randomized 1:1 to an aged control group (Aged; n = 8) and an EA treatment group (EA; n = 8). The 3-month-old rats served as young controls (Young). EA rats received EA at ST36, SP6, GB34 and SP10 bilaterally for 30 min a day, 5 days a week, for 8 weeks. EA significantly increased serum markers of bone formation in Aged rats. There were no significant differences in serum markers of bone resorption between EA and Aged rats. Deterioration of bone mineral density (BMD) and trabecular bone architecture was observed in the Aged group, while EA significantly increased BMD of the left femur and L5 vertebral body in aged rats. Aging-induced deterioration of trabecular bone architecture was partially reversed in EA rats. Runx2 and Osterix mRNA and protein levels were significantly increased and peroxisome proliferator-activated receptor (PPAR)γ was significantly decreased in bone marrow cells in EA compared with Aged groups. The mRNA and protein levels of core constituents of the Wnt/β-catenin signaling pathway (Wnt3a, low-density lipoprotein receptor-related protein (LRP)5 and β-catenin) were significantly increased and Dickkopf 1 was significantly decreased in bone marrow cells in EA compared with Aged groups. EA may prevent bone loss and deterioration in aged rats by promoting osteogenesis via a mechanism that may involve activation of the Wnt/β-catenin signaling pathway. EA may represent a therapeutic option for senile osteoporosis.

Osteoporosis and Normocalcemic Primary Hyperparathyroidism (Conservatively or Surgically Managed)

Asymptomatic primary hyperparathyroidism (PHPT) involves 80–90% of the parathyroid tumor-associated cases of PHPT in the modern medical era, while normocalcemic PHPT (NPHPT) has a prevalence of 0.1–11%. We aimed to analyze the bone status and mineral metabolism in NPHPT amid conservative or surgical management. In this narrative review, we searched PubMed (between January 2020 and July 2024) via different keywords. Fourteen studies from the final analysis (388 patients with NPHPT; 1188 with PHPT; and 803 controls) showed that mean serum calcium levels varied between 2.57 and 2.26 mmol/L in NPHPT. Ten studies identified a similar 24 h urinary calcium in NPHPT versus hypercalcemic PHPT (HPHPT). Except for one study, a mandatory vitamin D analysis was performed, but the 25-hydroxyvitamin D cut-offs varied. Osteoporosis (n = 6 studies; N = 172 with NPHPT) was confirmed in 41.7–100% of NPHPT subjects. In surgery candidates, this rate might be overestimated. A DXA analysis was performed in eight studies (235 subjects with NPHPT, and 455 patients with HPHPT); two studies identified a lower BMD in HPHPT &lt; NPHPT, but the results were not homogenous. A single study analyzed the TBS and found similar results in NPHPT. The prevalence of fractures (n = 9) varied between 7.4% and 42.8% in NPHPT. Bone turnover markers (N = 262 patients, n = 8 studies) showed lower bone formation markers in NPHPT versus PHPT (n = 3). Two studies analyzed the BMD and bone turnover markers following parathyroidectomy (161 patients, including 30 patients with NPHPT; mean ages over 60 years). To conclude, given the wide spectrum of complications associated with PHPT, an early diagnosis and proper management is essential. A more extensive screening in patients with osteoporosis and kidney stones might lead to the discovery of NPHPT, a more recently described form of PHPT. While it is still unclear whether NPHPT is an early stage of HPHPT or a separate entity, recent findings show similar osteoporosis and fracture occurrence, and an improvement in bone metabolism, following parathyroidectomy. More extensive prospective studies are crucial to understand the natural course of the disease, to reach a consensus regarding parathyroidectomy indications and surgery candidates’ selection, and to ensure proper personalized management for these patients. With the evolving diagnosis methods, PHPT has become a condition with a changing clinical presentation, which now requires modern evaluation and treatment approaches.

Expression of osteopontin and osteocalcin in Osteoblast cells exposed to a combination of polymethylmethacrylate (PMMA) and hydroxyapatite (HAp): A prospective observational study.

The success of implant placement will depend on the ability of the implant material to integrate with the surrounding tissue. Polymethylmethacrylate (PMMA) has been used as an implant material, but it has several fallback properties in its interaction with bone tissue. The addition of hydroxyapatite (HAp) to PMMA is expected to produce reinforced bioceramic polymers with better mechanical and biological properties. The purpose of this study was to evaluate the expression of osteopontin and osteocalcin in cultured osteoblasts when exposed to two implant candidate materials: PMMA-HApGMP, derived from bovine bone and processed under Good Manufacturing Practice by a Tissue Bank, and PMMA-HApBBK, sourced from limestone (CaCO3) and processed by Balai Besar Keramik. Twenty-four fetal rat calvariae osteoblast cell cultures were randomly divided into 6 groups: 7- and 14-day control group, 7 and 14 days PMMA-HApGMP group, 7 and 14 days PMMA-HApBBK group. The expression of osteopontin and osteocalcin was seen by immunocytochemical examination. The results showed that the average expression of osteopontin and osteocalcin in the treatment group on the 7th and 14th days was higher than the control group. The expression of osteopontin and osteocalcin in the PMMA-HApGMP group increased significantly (P < .05) on day 14. The PMMA-HAp combination material can accelerate the process of osteoblast differentiation which is characterized by an increase in osteopontin and osteocalcin which are markers of bone formation. This will support in increasing osseointegration.

Improvement of Bone Metabolism in Prepubertal Girls with Turner Syndrome Following Long-term Pegylated Growth Hormone Treatment.

The study aims to assess the improvement in bone metabolism in prepubertal girls with Turner Syndrome (TS) after long-term polyethylene glycol recombinant human Growth Hormone (PEG-rhGH) treatment. A 12-month longitudinal prospective study was conducted with 28 prepubertal girls diagnosed with TS. Participants were divided into two groups: 18 received PEG-rhGH therapy (0.1-0.25 mg/kg/week) and 10 did not. Anthropometric measurements, bone turnover markers (BTMs), and serum levels of IGF-1, calcium, and phosphate were collected at baseline and after 12 months. BTMs included bone alkaline phosphatase (BAP), Type I collagen propeptide (CICP), Type I collagen telopeptide (CTX), and fibroblast growth factor 23 (FGF23). After 12 months of PEG-rhGH therapy, the treatment group showed significant increases in growth velocity (GV) and height standard deviation scores (HtSDS). Serum IGF-1 levels increased rapidly within one month and remained elevated. BTMs indicated enhanced bone formation, significantly increasing BAP and CICP, while CTX levels remained low. FGF23 levels initially rose slightly but declined below baseline by 12 months. Elevated blood phosphate levels were observed. PEG-rhGH therapy in children with TS significantly improves linear growth and enhances bone formation markers, benefiting bone metabolism.

The Effects of the AGE Inhibitor Pyridoxamine on Bone in Older Women with Type 2 Diabetes: a Randomized Clinical Trial.

Type 2 diabetes (T2D) patients have reduced bone turnover and increased fractures. Advanced glycation endproducts (AGEs) impair osteoblasts and are implicated in diabetic fractures. Pyridoxamine (PM) is a vitamin B6 metabolite which inhibits formation of AGEs. We hypothesized that PM treatment in older T2D patients, by inhibiting AGEs, would increase bone formation. Double-blind RCT. Academic center. Older T2D women (n=55). Oral PM 200 mg twice daily for one year. The primary outcome was the change in the bone formation marker P1NP. Other outcomes were changes in bone resorption, bone mineral density (BMD), HbA1c and skin autofluorescence (SAF), and in a bone biopsy sub-group, the correlation between bone fluorescent AGEs (fAGEs) and SAF. P1NP increased 23.0% with PM (95% CI: 9, 37; within-group p=0.028) vs. 4.1% with placebo (-9, 17; within-group p=0.576; between-groups p=0.056). BMD increased at the femoral neck (PM: 2.6±5% vs. placebo: -0.9±4%; between-groups p=0.007). Bone resorption markers and SAF did not change. HbA1c decreased (PM: -0.38 ± 0.7% vs. placebo: 0.05 ± 1.7%; between-groups p =0.04). Within the PM group, the HbA1c change correlated inversely with the % P1NP change (r =-0.50, p=0.034). Cortical bone biopsy fAGEs correlated with SAF (r=0.86, p=0.001). Adverse events were similar between groups. PM tended to increase P1NP in older T2D women, as well as increasing bone density and reducing HbA1c. Further studies are needed to investigate the potential of PM as a disease mechanism-directed approach to reduce fractures in T2D.

6483 Diaphyseal Medullary Stenosis With Malignant Fibrous Histiocytoma: A Rare Skeletal Dysplasia/Sarcoma Syndrome

Abstract Disclosure: A. Grover: None. C.R. Ferreira: None. R.I. Gafni: None. S. Jumani: None. M.T. Collins: None. K.L. Roszko: None. I.R. Hartley: None. Introduction: Diaphyseal medullary stenosis with malignant fibrous histiocytoma (DMS-MFH) is a rare autosomal dominant syndrome associated with pathologic fractures, myopathy, premature hair graying, and aggressive osteosarcomas. DMS-MFH has been linked to genetic variants in the methylthioadenosine phosphorylase (MTAP) gene, which encodes an enzyme in the methionine salvage and polyamine synthesis pathway. This pathway is implicated in other skeletal fragility disorders, such as Snyder-Robinson syndrome, suggesting a still undefined role of this pathway in bone biology. We describe a kindred with DMS-MFH and identify diagnostic challenges. Case: A 53-year-old perimenopausal woman presented with four fragility fractures over one year. Relevant history included premature hair graying, esophageal strictures, and nephrolithiasis. The patient’s bone formation markers were slightly elevated; bone resorption markers were within reference range. Her only osteoporosis risk factor was perimenopausal status. Bone series showed a diffuse heterogeneous appearance of the long bones with a mixed lytic/sclerotic appearance. DEXA scan revealed osteopenia. Family history was significant for 2 sons with aggressive osteosarcomas diagnosed in their late teens; one died at age 20. The other son is currently 39-years-old with recurrent osteosarcomas in three different limbs. The family also has a multigenerational history of severe bone fragility, muscle weakness, and premature hair graying. The patient, her living son, and his father underwent genome sequencing that identified a variant in MTAP (c.885A&amp;gt;G; p.(R295=)) in the patient and son. This variant was previously reported in three other families with DMS-MFH and has been shown to alter splicing. Notably, commercial genetic testing did not report this as a relevant variant, and diagnosis required independent analysis of the raw sequence data. Based on these findings, the patient and her son were diagnosed with DMS-MFH. Given the bone fragility with elevated bone turnover markers we treated the patient with yearly zoledronic acid infusions with no subsequent fractures. Surveillance for osteosarcoma is also being performed with annual whole-body MRI. Conclusion: DMS-MFH has been reported in only five families to date. The sixth family described here has clinical characteristics similar to the other kindreds. Due to high risk of aggressive osteosarcoma, timely diagnosis is imperative to decrease morbidity and mortality. Commercial genome sequencing may miss this diagnosis, so targeted genetic testing should be pursued. As more cases are identified, characterization of affected families may enhance our understanding of the natural history of the disease and guide surveillance and treatment strategies. Presentation: 6/2/2024

Osteogenic effect of alogliptin in chemical-induced bone loss: a tri-modal in silico, in vitro, and in vivo analysis.

To investigate the effects of Alogliptin in chemical-induced post-menopausal osteoporosis. The binding affinity of alogliptin with osteogenic proteins was analysed in silico. The effect of alogliptin on osteogenic proteins and mineralization of osteoblastic cells was evaluated in UMR-106 cells. Further, in vivo anti-osteoporotic activity of alogliptin was evaluated in postmenopausal osteoporosis. Various bone turnover markers were assayed in serum. This followed the analysis of microarchitecture of bone, histology, and immunohistochemistry (IHC) of bone tissue. Docking scores showed that alogliptin has binding affinity for bone alkaline phosphatase (BALP), osteocalcin, and bone morphogenic protein (BMP-2). Alogliptin also enhanced mineralization of osteoblast cells, evidenced with increased ALP, osteocalcin, and BMP-2. Animal studies revealed significant elevation of bone formation markers, bone ALP, osteocalcin and BMP-2, and decreased bone resorption markers, receptor activator of NF-κβ (RANKL), cathepsin K (CTSK), tartrate resistant acid phosphatase (TRAcP5b) in VCD-induced post-menopausal osteoporosis. Micro computed tomography (μCT) analysis and histology of femur bone and lumbar vertebrae demonstrated decrease in trabecular separation and improved bone density. IHC of femur showed reduced DPP4 enzyme. Alogliptin increased mineralization in osteoblast cells. It had beneficial effects also altered bone turnover markers, repaired the trabecular microstructure, improved bone mineral density, and exhibited bone forming capacity targeting DPP-4 enzyme in postmenopausal osteoporosis.

The Effect of Photobiomodulation on Bone Mineral Density, Serum Vitamin D, and Bone Formation Markers in Individuals with Complete Spinal Cord Injuries with Osteoporosis.

Study design: A quasi-experimental study utilized a matched-pair design, administering photobiomodulation at four-sites on one side of the body and assigning control to the other side at corresponding sites. Objectives: This study aimed to assess photobiomodulation treatment effects on bone mineral density (BMD) measurement using dual-energy X-ray-absorptiometry in individuals with complete spinal cord injury (C.SCI) and osteoporosis. Methods: Eight patients received treatment at four-sites: forearm-mid-distal (MID), proximal-femur, distal-femur, and proximal-tibia, totaling 32 sites. Using an 830 nm gallium-aluminum-arsenide semiconductor laser irradiation was administered three times weekly for 8 weeks. Different doses (energy density) were determined depending on bone depth from skin surface, as assessed by sonography and adjusted through irradiation time to be 8, 10, and 12 J/cm2 for depths <1 cm, between 1 and 1.5 cm, and >1.5 cm, respectively, using 200 mW power to deliver the optimal isodose of laser at each depth of bone within each therapeutic site. BMD was measured at baseline, week 8 of treatment, and week 15 of follow-up. Serum 25-(OH)-vitamin D and bone formation markers including osteocalcin and bone-alkaline-phosphatase (B-ALP) were also assessed at baseline and week 8 of treatment. Results: Significant increases in BMD were noted in proximal-femur and forearm-MID at both week 8 and week 15. Serum 25-(OH)-vitamin D levels significantly increased after treatment. However, no notable changes were observed in distal-femur and proximal-tibia BMD or in osteocalcin and B-ALP levels. Conclusions: Photobiomodulation (830 nm) laser demonstrated efficacy in improving BMD at proximal-femur and forearm-MID in individuals with C.SCI. Moreover, the observed positive influence on vitamin D levels suggests a potential photobiomodulation role, warranting further investigation.

Comparison of Denosumab with Romosozumab in the treatment of male osteoporosis: a retrospective cohort study

We aimed to investigate the efficacy of romosozumab treatment compared with that of denosumab in especially male osteoporosis patients. This retrospective cohort study included 174 Japanese male patients receiving either denosumab or romosozumab for 12 months. Propensity score matching extracted 50 patients per treatment group for standardization of group characteristics. The endpoints include the rate of change in the bone mineral density (BMD) of the lumbar spine, total hip, and femoral neck after 12 months of treatment as well as the changes in serum bone metabolism markers. The mean 12-month percentage increase in the lumbar spine BMD from baseline was significantly greater with romosozumab (13.0% ±1.7%) than with denosumab (4.5%±0.6%) (P < 0.01). The total hip and femoral neck BMD exhibited a similar trend at 12 months; however, no significant between-group differences were observed. With denosumab, bone formation, and resorption marker levels significantly decreased at 6 and 12 months. Conversely, with romosozumab, the levels of bone formation markers increased transiently at 6 months before returning to baseline, whereas bone resorption markers significantly decreased at both time points. Romosozumab demonstrated significantly superior effects over denosumab in improving BMD, especially of the lumbar spine, suggesting that romosozumab can be used for treating male osteoporosis.

Preventing osteoporotic bone loss in mice by promoting balanced bone remodeling through M-CSFRGD, a dual antagonist to c-FMS and αvβ3 receptors

Osteoporosis is a common, age-related disease caused by imbalanced bone remodeling. Current treatments either shut down bone resorption or robustly stimulate bone formation. Here, we describe a novel compound that inhibits osteoclast activity without causing apparent disruptions to bone formation by targeting both c-FMS (i.e., osteoclast differentiation) and αvβ3 integrin (i.e., osteoclastic bone resorption) receptors. We show that human serum albumin (HSA)-conjugated M-CSFRGD protein (M-CSFRGD-HSA) effectively inhibits the activity of both receptors, with a three-fold higher serum half-life compared to the unconjugated M-CSFRGD. We then treated ovariectomized mice with different doses of M-CSFRGD-HSA, alendronate, or a monospecific control protein. The bispecific M-CSFRGD-HSA was superior to a monospecific control in alleviating bone loss and reducing osteoclast distribution and function. M-CSFRGD-HSA and alendronate effectively prevented ovariectomy-induced bone loss, but M-CSFRGD-HSA had a milder inhibitory effect on osteoclast distribution and activity. Moreover, alendronate halted bone formation, while M-CSFRGD-HSA-treated mice showed an increased level of serum amino-terminal propeptide of type I collagen, a bone formation marker. Our data indicate that the mild reduction in osteoclast activity facilitated by the bispecific M-CSFRGD-HSA allows the maintenance of certain levels of bone formation and may be superior to treatments that induce osteoclast depletion.

Iron Deficiency Is Associated with Elevated Parathormone Levels, Low Vitamin D Status, and Risk of Bone Loss in Omnivores and Plant-Based Diet Consumers.

A cross-sectional study was performed in healthy adults (mean age 28 y, 67% women) whose habitual diet was an omnivore, lacto-ovo vegetarian, or vegan diet. The total sample (n = 297) was divided into two groups according to the parathormone (PTH) cut-off value of 65 pg/mL of either normal-PTH (n = 228) or high-PTH (n = 69). Vitamin D status (25-hydroxycholecalciferol, 25-OHD), PTH, and bone formation (bone alkaline phosphatase, BAP) and bone resorption (N-telopeptides of type I collagen, NTx) markers were determined. Hematocrit, erythrocytes, hemoglobin, platelets, serum iron, serum transferrin, transferrin saturation, and serum ferritin were also measured. In the total sample, 25-OHD and PTH were negatively correlated, and all subjects with high PTH presented vitamin D insufficiency (25-OHD < 75 nmol/L). High bone remodeling was observed in the high-PTH group, with significantly higher NTx and marginally higher BAP compared to the normal-PTH group. Hematocrit and ferritin were significantly lower in the high-PTH compared to the normal-PTH group. However, serum iron was higher in the high-PTH group, which was only observed for the lacto-ovo vegetarian and vegan subjects. It is concluded that both low vitamin D and low iron status are associated with elevated PTH and bone resorption, more in vegetarians than omnivores, which is in line with the hypothesis that chronic iron deficiency in adulthood mainly predisposes to osteoporosis in postmenopausal women and the elderly.

Evaluation of the systemic effect of bone formation marker released by endodontic calcium silicate-based sealers in local tissues, the bloodstream, and body organs

Evaluation of the systemic effect of bone formation marker released by endodontic calcium silicate-based sealers in local tissues, the bloodstream, and body organs

The short-chain fatty acid receptors Gpr41/43 regulate bone mass by promoting adipogenic differentiation of mesenchymal stem cells.

Bone is a dynamic tissue that is constantly remodeled throughout adult life. Recently, it has been shown that bone turnover decreases shortly after food consumption. This process has been linked to the fermentation of non-digestible food ingredients such as inulin by gut microbes, which results in the production of the short-chain fatty acids (SCFAs) acetate, propionate and butyrate. SCFAs exert various metabolic functions, which in part can be explained by activation of G protein-coupled receptors (Gpr) 41 and 43. However, the potential relevance of a SCFA-Gpr41/43 signaling axis for bone metabolism has not been established. The aim of our study is to investigate the role of Gpr41/43 in bone metabolism and osteogenic differentiation of mesenchymal stem cells. For this purpose, we analyzed the skeletal phenotype of wild type controls (WT) and Gpr41/43 double knockout (Gpr41/43 dKO) mice fed either a chow or an inulin-enriched diet. In addition, we isolated bone marrow derived mesenchymal stem cells from WT and Gpr41/43 dKO mice and differentiated them into osteoblasts in the absence or presence of acetate. MicroCT scanning of femoral bones of Gpr41/43 dKO mice revealed a significant increase of trabecular bone volume and trabecular compared to WT controls. Treatment of WT bone marrow-derived osteoblasts with acetate resulted in decreased mineralization and substantial downregulation of bone formation markers such as Phex, Ptgs2 and Col1a1. Notably, this effect was strongly attenuated in differentiated osteoblasts lacking Gpr41/43. Inversely, acetate supplementation resulted in higher levels of adipocyte marker genes including Pparg, Lpl and Adipoq in bone marrow-derived cells from WT mice, an effect blunted in differentiated cells isolated from Gpr41/43 dKO mice. Overall, these data indicate that acetate regulates bone architecture via SCFA-Gpr41/43 signaling by modulating the osteogenic versus adipogenic differentiation of mesenchymal stem cells.

Effects of tofacitinib on bone turnover markers and bone modulators in patients with rheumatoid arthritis

Key-pointsBone turnover makers (P1nP, B-ALP, CTX), bone modulators (Dkk1, sclerostin) and BMD were measured prospectively in rheumatoid arthritis patients treated with tofacitinib.Sclerostin increased significantly after treatment with tofacitinib, P1nP and B-ALP (markers of bone formation) decreased significantly.

Effects of Glucagon-Like Peptide-1 Receptor Agonist on Bone Mineral Density and Bone Turnover Markers: A Meta-Analysis.

Glucagon-like peptide-1 receptor agonist (GLP-1RA) may promote bone formation, but conversely, they could also weaken bones due to the reduction in mechanical load associated with weight loss. However, the clinical effects in humans have not been clearly demonstrated. This meta-analysis aimed to evaluate whether GLP-1RAs affect BMD and bone turnover markers. PubMed, Embase, and Scopus were searched on June 13, 2024. The eligibility criteria were: (1) human studies, (2) receiving a GLP-1RA for more than 4weeks, (3) an untreated control group or a placebo group, (4) reporting of at least one BMD or bone turnover marker, and (5) an RCT design. The risk of bias was assessed using the Cochrane risk of bias 2 tool. Fixed- or random-effects meta-analysis was performed according to heterogeneity. Seven studies were included in the meta-analysis. GLP-1RAs did not significantly change BMD in the femoral neck (mean difference [MD], 0.01g/cm2; 95% CI, -0.01-0.04g/cm2), in the total hip (MD, -0.01g/cm2; 95% CI, -0.02-0.01g/cm2), and in the lumbar spine (MD, 0g/cm2; 95% CI, -0.02-0.02g/cm2). C-terminal telopeptide of type 1 collagen (CTX), a bone resorption marker, significantly increased after GLP-1RA treatment (MD, 0.04μg/L; 95% CI, 0.01-0.07μg/L). GLP-1RAs did not significantly change bone formation markers such as procollagen type 1 N-terminal propeptide, bone-specific alkaline phosphatase, osteocalcin. GLP-1RA did not affect BMD and bone formation markers. However, GLP-1RAs led to a significant increase in CTX.

Association between changes in serum bone metabolism markers and bone microarchitecture changes during basic combat training – The ARMI study

ImportanceU.S. Army Basic Combat Training (BCT) improves tibial volumetric bone mineral density (BMD) and structure in most, but not all soldiers. Few studies have investigated whether changes in serum bone biomarkers during BCT are associated with changes in tibial BMD and bone structure following BCT. ObjectiveTo characterize bone biomarker changes during BCT and to investigate the relationship between changes in bone biomarkers and changes in tibial BMD and bone structure. MethodsWe enrolled 235 trainees entering BCT in this ten-week prospective observational study. Trainees provided fasted blood samples and questionnaires weekly throughout BCT. Procollagen type 1 N-terminal propeptide (PINP) and C-terminal telopeptide of type 1 collagen (CTX) were measured by enzyme-linked immunoabsorbent assays every two weeks during BCT. We evaluated body composition and mass via dual-energy X-ray absorptiometry and bone structure, microarchitecture, and mineral density at the distal tibia via high-resolution peripheral quantitative computed tomography at baseline and post-BCT. ResultsBoth male (n = 110) and female trainees (n = 125) were young (20.9 ± 3.7 and 20.7 ± 4.3 years, respectively), with normal to overweight BMIs (25.2 ± 4.1 and 24.2 ± 3.6 kg/m2, respectively). In female trainees, PINP increased during and post-BCT compared to baseline, with the greatest increase in PINP at week four (45.4 % ± 49.6, p < 0.0001), whereas there were no changes in CTX. PINP also increased in male trainees, but only at weeks two and four (21.9 % ± 24.5, p = 0.0027 and 35.9 % ± 35.8, p < 0.0001, respectively). Unlike female trainees, in males, CTX was lower than baseline at weeks four, eight, and post-BCT. The change in PINP from baseline to week four of BCT was positively associated with changes in tibial BMD, Tb.BMD, Tb.Th, Tb.BV/TV, Ct.Th, Ct.Ar, and Ct.Po from the baseline to post-BCT. ConclusionThe bone formation marker PINP increases during U.S. Army BCT, especially during the first four weeks. Increases in PINP, but not CTX, were correlated with improved BMD and bone structure in the distal tibia.