Resorption Markers Research Articles

Altered post-fracture systemic bone loss in a mouse model of osteocyte dysfunction

Abstract Femur fracture leads to loss of bone at uninjured skeletal sites, which may increase risk of subsequent fracture. Osteocytes, the most abundant bone cells, can directly resorb bone matrix and regulate osteoclast and osteoblast activity, but their role in systemic bone loss after fracture remains poorly understood. In this study we used a transgenic (TG+) mouse model that overexpresses human B-cell lymphoma 2 (BCL-2) in osteoblasts and osteocytes. This causes enhanced osteoblast proliferation, followed by disruption in lacunar-canalicular connectivity and massive osteocyte death by 10 weeks of age. We hypothesized that reduced viable osteocyte density would decrease the magnitude of systemic bone loss after femur fracture, reduce perilacunar remodeling, and alter callus formation. Bone remodeling was assessed using serum biomarkers of bone formation and resorption at 5 days post-fracture. We used micro-computed tomography, high resolution x-ray microscopy, mechanical testing, and Raman spectroscopy to quantify the magnitude of systemic bone loss, as well as changes in osteocyte lacunar volume, bone strength, and bone composition 2 weeks post-fracture. Fracture was associated with a reduction in circulating markers of bone resorption in non-transgenic (TG-) animals. TG+ mice exhibited high bone mass in the limbs, greater cortical elastic modulus and reduced post-yield displacement. After fracture, TG+ mice lost less trabecular bone than TG- mice, but conversely TG+ mice exhibited trends towards a lower yield point and reduced femoral cortical thickness after fracture, though these were not statistically significant. Lacunar density was greater in TG+ mice, but fracture did not alter lacunar volume in TG+ or TG- mice. These findings suggest that osteocytes potentially play a significant role in the post-traumatic systemic response to fracture, though the effects differ between trabecular and cortical bone.

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.

Maltobionic acid protects against ovariectomy‐induced osteoporosis by suppressing bone resorption

AbstractBackgroundOsteoporosis is a debilitating disease characterized by decreased bone density. In this study, we evaluated the anti‐osteoporotic effect of maltobionic acid (MB), one of the components of honey, and calcium maltobionate (MBCa) on bone density and metabolism using a mouse model of osteoporosis. The underlying mechanisms of MB and MBCa action were also investigated.ResultsOvariectomized (OVX) mice were fed diet containing MB or MBCa for 80 days, and femoral bone mineral content and mineral density (BMD) were evaluated. As expected, OVX reduced BMD; however, the administration of MB and MBCa significantly prevented this decrease. Furthermore, MB and MBCa treatment significantly reduced the serum levels of tartrate‐resistant acid phosphatase 5b (TRACP‐5b), a bone resorption marker, and significantly increased the levels of serum calcitonin, compared to those in the OVX control group. In vitro, the relatively high‐dose levels of MB and MBCa inhibited osteoclast differentiation by decreasing the protein expression of nuclear factor of activated T‐cell cytoplasmic 1 (NFATc1), the master transcription factor of osteoclastogenesis.ConclusionOur results showed that osteoporotic mice treated with MB and MBCa had improved bone density and bone metabolism compared to the OVX controls. Moreover, it was hypothesized herein that the suppressive effect on osteoclast differentiation slightly contributed to these results concomitantly. These findings suggest that the intake of MB or MBCa may contribute to the maintenance of bone health, including the prevention of primary osteoporosis.

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

9172 Contrasting Bone Profiles In Pcos Are Related To Bmi: A Systematic Review And Meta-analysis

Abstract Disclosure: M.O. Premaor: None. G. Risseti: None. J. Piovezan: None. F.V. Comim: None. Polycystic ovary syndrome (PCOS) is a complex and multifaceted disorder that may affect bone health. Controversial results have emerged regarding whether PCOS is protective or increases the risk of bone frailty. We conducted a systematic review and meta-analysis of published research on bone mineral density (BMD), bone markers, and the risk of fractures in individuals with PCOS. We searched MEDLINE, Embase, and conference s and preprints. Studies were eligible if the PCOS was defined according to the NIH criteria, the Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group criteria, AE-PCOS society criteria, or ICD codes. The endpoints studied included fractures, bone mineral density (BMD), and bone markers. The study protocol is available at PROSPERO (CRD42016049664). From the 3322 studies identified in the databases, 111 had their full texts evaluated, and 31 studies met the inclusion criteria for qualitative analysis. Overall, cross-sectional studies included 1822 individuals with PCOS and 1374 controls, while cohort studies incorporated 30305 women with PCOS and 101907 controls. No differences were observed between individuals with PCOS and the control group in the pooled analysis for the whole group. Nevertheless, contrasting profiles emerged after stratification using a BMI cutoff of 27 kg/m2. Women with PCOS and a mean BMI &amp;lt;27 kg/m2 exhibited lower spine BMD (MD -0.060; 95% CI, -0.110 and -0.011) and total hip BMD (MD -0.042; 95% CI, -0.068 and -0.017), and increased bone resorption marker (CTX) levels (SMD 0.38; 95%CI 0.03 and 0.72). Conversely, women with PCOS and a mean &amp;gt;27 kg/m2 exhibited increased spine BMD (MD 0.029; CI 95%, 0.009 to 0.048) and total hip BMD (MD 0.036; CI 95%, 0.010 to 0.063), with no significant changes in bone resorption markers. Due to the limited number of longitudinal studies available, it was not possible to determine the risk of bone fractures in both groups. In conclusion, the findings of this systematic review show a negative impact of PCOS on bone health in women with a BMI &amp;lt;27 kg/m2, suggesting that increased surveillance and research for bone disease may be necessary for this particular group. Presentation: 6/3/2024

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.

Biomarkers of bone metabolism in [223Ra] RaCl2 therapy - association with extent of disease and prediction of overall survival

BackgroundThe alpha-emitting radionuclide therapy [223Ra]RaCl2 (Radium-223) improves overall survival (OS) and time to symptomatic skeletal event (SSE) in patients with metastatic castration-resistant prostate cancer (mCRPC). Evidence suggests that the effect of Radium-223 is partly exerted through an impact on the surrounding bone matrix. We hypothesized that bone metabolism markers (BMM) could provide predictive information regarding response to Radium-223. Accordingly, the aim of this study was to investigate changes in BMM during Radium-223 therapy and evaluate association with clinical outcome.MethodsProspective study of BMM in patients with mCRPC receiving Radium-223. Blood samples were collected before each administration of Radium-223 and the following BMM were quantified; bone-specific alkaline phosphatase (BALP), osteocalcin, procollagen type I N-propeptide (PINP), C-terminal telopeptide of type I collagen (CTX), C-terminal cross-linking telopeptide of type I collagen generated by matrix metalloproteinases (CTX-MMP), tartrate-resistant acid phosphatase isoform 5b (TRACP5b), receptor-activated nuclear factor κB ligand (RANKL), osteoprotegerin (OPG), and sclerostin. Clinical outcomes were scintigraphic progression during/after therapy, change in bone scan index (BSI), occurrence of SSE, and OS.ResultsA total of 55 mCRPC patients were included. There was a significant linear association between skeletal extent of disease and CTX-MMP, PINP, BALP, and osteocalcin. No significant association between dynamics in BSI and BMM were detected. Median OS for the cohort was 14 months (95% CI: 10.7–16.8). Baseline levels of Log2-CTX-MMP (HR = 2.15 (95%CI: 1.1–4.1)) and Log2-BALP (HR = 1.59 (95%CI: 1.1–2.1)) were associated with OS. Patients with increasing CTX-MMP during therapy had significantly shorter OS (Median OS = 4 mo. (95%CI: 2.3–5.7)) than patients with stable or decreasing CTX-MMP (Median OS = 12 mo. (95%CI: 10.1–13.9), P < 0.001).ConclusionBMM are significantly associated with scintigraphic extent of skeletal disease and OS in patients with mCRPC. Particularly, the bone resorption marker CTX-MMP is a promising surrogate marker for prediction of outcome in patients receiving Radium-223 therapy and could potentially improve selection of patients for therapy and assessment of response.Trial registrationClinicaltrials.gov, NCT03247010. Registered 10th of August 2017, https://clinicaltrials.gov/study/NCT03247010?term=NCT03247010&rank=1.

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.

6795 Romosozumab improves bone mineral density and markers of bone resorption in a patient with osteogenesis imperfecta

6795 Romosozumab improves bone mineral density and markers of bone resorption in a patient with osteogenesis imperfecta

Elevated Bone Turnover Markers After One Infusion Of Zoledronic Acid Post Denosumab Cessation

Abstract Background Denosumab is a commonly used to treat osteoporosis though should not be stopped without transitioning to bisphosphonates to reduce the risk of rebound bone loss and fracture. Recent NOGG guidelines recommend IV zoledronic acid (ZA) six months after the last denosumab injection with further infusions based on bone turnover markers (BTM). Methods We collated data (over the past 5 years) on the first follow up BTM measured after zoledronic acid treatment given to patients where denosumab was stopped. ZA was administered between 6-7 months after the last denosumab injection. The bone resorption marker (C-Telopeptide type I collagen, CTX ng/ml) was measured at different time points: 4 months, 4-6 months, and between 6-12 months. A subtherapeutic CTX was defined as &amp;gt; 0.300 ng/ml. Results There were 95 patients, 93% female, mean age 67.8 years and duration of denosumab therapy 4.6 years. Bone markers were significantly elevated from baseline at all timepoints. Mean CTX at 4 months was 0.450, 6 months 0.470 and 6-12 months 0.65. Overall, 45% had a subtherapeutic CTX at 4 months, 45% at 6 months and 70% between 6-12 (mean 9 months) and this was predicted by time from first ZA infusion (P=0.03). Conclusion Nearly half of patients had subtherapeutic BTM at 4-6 months and the majority at 6-12 months after receiving ZA. For patients on denosumab therapy for a similar duration (4-5 years), our results support the routine administration of a second ZA six months after their first ZA. Delays in administering a second infusion may result in a substantial rise in bone resorption markers and significant bone loss. This highlights the need for timely access to ZA for such patients transitioning off denosumab therapy.

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.

Erosion regression in patients with rheumatoid arthritis after upadacitinib-a pilot study using high resolution peripheral quantitative computed tomography.

To evaluate whether inhibition of Janus kinases (JAK) 1 could lead to erosion repair on high-resolution peripheral quantitative computer tomography (HR-pQCT) in patients with active rheumatoid arthritis (RA). This was a prospective, non-randomized pilot study. We enrolled 20 adult patients with active RA with ≥1 bone erosion on HR-pQCT. They were given upadacitinib 15 mg once daily for 24 weeks. HR-pQCT of the metacarpophalangeal joint was performed at baseline and 24-week. The serum bone biomarkers level was evaluated before and after treatment. Twenty age-and-sex matched RA patients from another study treated with conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) were included as active controls. Nineteen patients in the upadacitinib group completed the study procedures. After 24 weeks, despite similar improvement in disease activity, a reversed trend in the mean erosion volume change on HR-pQCT was observed comparing the upadacitinib and active control group (upadacitinib group: -0.23 ± 3.26mm3 vs control group: 1.32 ± 6.05mm3, p= 0.131). A greater proportion of erosions in the upadacitinib group demonstrated regression (27% vs 12%, p= 0.085). Using general estimating equation (GEE), the use of upadacitinib was significantly associated with erosion regression (OR: 3.61, 95% CI: 1.00-13.00, p= 0.049) after adjusting for the difference in disease duration. The serum levels of bone resorption markers reduced after upadacitinib treatment. No new safety signal was noted. Despite a similar improvement in RA disease activity after upadacitinib compared with csDMARDs, a differential regression of erosion on HR-pQCT was observed in patients received upadacitinib. The potential role of JAK1 inhibition in erosion repair should be investigated.

POLYCYSTIC OVARY SYNDROME AND BONE TURNOVER IN POSTMENOPAUSAL WOMEN

Considering the metabolic and hormonal changes associated with polycystic ovary syndrome (PCOS), their potential affect bone health has been proposed. The aim of the current study was to evaluate the effect of several hormonal and metabolic alterations associated with polycystic ovary syndrome on bone in postmenopausal women. Materials and methods: The study included 56 patients with PCOS and 42 women without this disease aged 50–65 years. Dual-energy X-ray absorptiometry was used to measure bone mineral density (BMD) of the lumbar spine and femoral neck. Serum levels of amino-terminal propeptide of procollagen 1 (P1NP) and carboxy-terminal telopeptide of type I collagen (b-CTx), as well as levels of parathyroid hormone (PTH), vitamin D (25(OH)D3), anti-Mullerian hormone (AMH), insulin, testosterone (T), 17-hydroxyprogesterone (17-OHP), dehydroepiandrostenedione sulfate (DHEAS), follicle stimulating hormone, luteinizing hormone, and estradiol were determined. The HOMA-IR index and anthropometric indicators were calculated. Statistical data were analyzed by nonparametric testing using BioStat Pro 6.2.2.0 software (AnalystSoft Inc., Walnut, USA). Quantitative data are presented as median and quartiles 1 and 3 (Me [Q1; Q3]); The significance of intergroup differences was established using the Mann–Whitney U test (p&lt;0.05). To identify relationships between indicators, a univariate analysis was carried out with the calculation of the Spearman rank correlation coefficient (r). Results. Women with PCOS had late-onset menopause (p=0.007) and a higher body mass index (BMI, p=0.009) than the control group. Additionally, women with PCOS had higher levels of DHEAS, total T, and 17-OHP than controls. P1NP and b-CTx were significantly different from controls (p=0.028 and p=0.032, respectively). A direct relationship was found between BMI and the activity of the resorption marker b-CTx (r=0.342, p=0.002) and an inverse collinear relationship between AMH values with b-CTx (r=–0.507, p=0.001). BMD in PCOS was higher compared to controls. An inverse relationship exists between BMD of L1–L4 and b-CTx level (r=–0.387, p=0.026) and positive with insulin (r=0.267, p=0.042), AMH (r=0.561, p=0.031) and testosterone (r=0.458, p=0.039). Higher DHEAS levels were associated with higher femoral neck BMD (r=0.473, p=0.035). P1NP was negatively correlated with femoral neck BMD (r=-0.429, p=0.038). Conclusions. Bone mineral density in women with polycystic ovary syndrome declines more slowly with age compared to their peers, possibly due to the effects of excess androgens and insulin. In postmenopausal women with polycystic ovary syndrome, metabolic processes in bone tissue accelerate, while bone resorption exceeds bone formation. Thus, women affected by polycystic ovary syndrome may be considered at risk of developing osteopenic syndrome.

The diagnostic and prognostic value of tartrate-resistant acid phosphatase isoform 5b for giant cell tumor of bone.

Serum level of tartrate-resistant acid phosphatase 5b (TRACP5b) is an excellent serum marker of bone resorption. In patients with giant cell tumor of bone (GCTB), TRACP5b levels are reportedly elevated. This study investigated whether TRACP5b could be a diagnostic serum marker and be useful for detecting postoperative disease progression for GCTB. Cohort 1: We abstracted data from 120 patients with TRACP5b measurements from our database: 49 patients with GCTB and 71 patients non-GCTB. We compared serum TRACP5b values between the GCTB and non-GCTB groups. Cohort 2 included 47 patients with GCTB who had more than 6months of follow-up and multiple TRACP5b values. For patients with local recurrence, TRACP5b change rate was calculated by comparing the TRACP5b value just before progression (a) with the value at the time of progression (b): Change rate = [(b)-(a)]/(a). In the non-progression group, the change rate was calculated from the two consecutive TRACP5b values, (c) and (d): Change rate =[(c)-(d)]/(c). We compared TRACP5b change rates between the progression and non-progression groups. Cohort 1: The GCTB group had a significantly higher mean TRACP5b value (1756 ± 2021mU/dL) than the non-GCTB group (415 ± 219mU/dL) (p < 0.0001). Cohort 2: The mean TRACP5b change rate of the progression group was significantly higher than the non-progression group (8.53 ± 8.52 and 0.24 ± 0.27, respectively; p < 0.0001). TRACP5b is a useful diagnostic marker in GCTB. The rate of change in serum TRACP5b values is a highly sensitive marker for predicting local recurrence in GCTB.

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.

A non-invasive measure of bone growth in mammals: Validating urinary CTX-I as a bone resorption marker through long-bone growth velocity in bonobos.

Assessing bone growth trajectories in mammals is crucial for understanding life history dynamics, but the quantification of bone growth in natural settings can be challenging. Bone resorption markers that can be measured in urine, such as C-telopeptide of type I collagen (CTX-I), offer a non-invasive solution to assess bone growth. Although measurement of urinary CTX-I levels has been applied extensively in human studies, its use in other species is so far limited to a few clinical studies. To validate urinary CTX-I as a bone resorption marker under less controlled conditions, we investigated within-individual day-to-day variation, diurnal patterns, and sex and age-specific variation in zoo-housed bonobos (Pan paniscus). We then also correlated urinary CTX-I levels with forearm growth velocity measures. We found a day-to-day variability in urinary CTX-I levels of around 25%, comparable to human variation. Diurnally, CTX-I levels decreased, aligning with observations in humans and other species. Both sexes showed an age-related decline in urinary CTX-I levels, with a steady decrease after the age of 10 years. Additionally, we found a positive correlation between forearm growth velocity and urinary CTX-I levels across age in female, but not in male, bonobos. Our results demonstrate that urinary CTX-I levels are a meaningful measure of bone growth and highlight its potential to examine bone growth trajectories also in wild populations to investigate life history dynamics.