Chronic Bone Research Articles

Doença mineral e óssea da doença renal crônica em indivíduos em hemodiálise e a suas correlações com as condições clínicas, antropométricas e laboratoriais

Introduction: Chronic Kidney Disease-Mineral and Bone Disease is one of the main complications of individuals on hemodialysis. Objective: this research aims to analyze the correlations of the laboratory components of Chronic Kidney Disease-Mineral and Bone Disease with clinical, anthropometric and laboratory factors of individuals on hemodialysis. Methods: this is a cross-sectional study with 790 patients on hemodialysis, in southeastern Brazil. Chronic Kidney Disease-Mineral and Bone Disease was evaluated according to specific laboratory diagnostic criteria already defined in the literature. Assessment was carried out regarding the existence of a linear correlation between the dependent and independent variables. References used: r < 0.4 (weak correlation); r ≥ 0.4 and < 0.6 (moderate correlation); r ≥ 0.6 (strong correlation). The Significance level adopted was 5%. Results: parathyroid hormone and duration of renal replacement therapy showed a moderate positive correlation with each other (r 0.582, p <0.001). Phosphorus levels had a moderate positive correlation with potassium (r 0.556, p 0.020) and negative correlation with age (r -0.413, p 0.036). 25-hydroxyvitamin D levels had a positive correlation with adductor pollicis muscle thickness (r 0.602, p 0.018) and right hand grip strength (r 0.402, p <0.001), and a negative correlation with tricipital skinfold (r -0.600, p 0.020) and corrected arm muscle area (r -0.769, p 0.024). Ionic calcium levels had a strong positive correlation with duration of renal replacement therapy (r 0.961, p 0.015) and a strong negative correlation with Body Mass Index (r -0.82, p 0.046). Conclusion: all laboratory elements of Chronic Kidney Disease-Mineral and Bone Disease showed important correlations with clinical, anthropometric and laboratory components of individuals on hemodialysis.

Clinical management of hypophosphatemic osteomalacia induced by adefovir and tenofovir: Insights from a case report.

Hypophosphatemic osteomalacia is a rare chronic metabolic bone disease characterized by low serum phosphate levels owing to genetic or acquired causes. This article presents a case report of the clinical management, challenges encountered, and prognosis of secondary hypophosphatemic osteomalacia induced by defovir and tenofovir. A 55-year-old male patient had been experiencing persistent dull chest pain and fatigue for more than a year. The patient had chronic hepatitis B infection for over 10 years, with regular use of adefovir dipivoxil capsules for more than 10 years. Five months before admission, the patient was switched to tenofovir alafenamide fumarate tablets. After obtaining clinical manifestations, medical history, and examination results, tumor-induced osteomalacia was excluded, and the final diagnosis was drug-induced hypophosphatemic osteomalacia. Adefovir dipivoxil and tenofovir alafenamide were discontinued, and the patient was switched to entecavir disintegration tablets for antiviral therapy. He was advised to follow a high-phosphate diet, receive phosphorus supplementation and calcitriol capsules to promote calcium absorption, obtain moderate sun exposure, and take measures to prevent falls and fractures. Serum phosphate levels showed a gradual upward trend, with the most recent measurement being 0.85 mmol/L. The bone density gradually improved and reached normal levels in the most recent assessment. The symptoms of fatigue and chest pain were resolved. Accurate diagnosis requires a combination of clinical presentation, medical history, biochemical and radiological findings, and, if available, measurement of fibroblast growth factor 23 (FGF 23). The role of national, provincial, or regional centers for rare diseases is crucial for conducting unconventional tests and providing access to rare medications.

Gelombang Elektromagnetik ELF : Inovasi Baru dalam Terapi Kesehatan Tulang

Extremely Low Frequency (ELF) electromagnetic waves are increasingly recognized for their potential in treating bone health as a safe and effective non-invasive method. Studies have shown that ELF can stimulate osteoblast activity, increase bone density, and accelerate fracture healing. This article reviews the mechanism of ELF, its application in the treatment of osteoporosis, and its safety in clinical practice. With standardized parameters, ELF can be an innovative solution for chronic bone disorders or abnormalities, as well as providing great benefits in the medical world.

Profile and Phenotypes of Chronic Kidney Disease-Mineral and Bone Disorders in Chronic Haemodialysis Patients

Background: Chronic kidney disease-mineral and bone disorder (CKD-MBD) significantly affects haemodialysis patients, impacting prognosis and quality of life. This study examines CKD-MBD profiles and phenotypes to guide intervention strategies.Methods: We conducted a cross-sectional study at Dr. Soetomo Hospital, Surabaya, from August to October 2023, involving 111 haemodialysis patients. Data collected included demographic characteristics, CKD etiology, nutritional status, and bone mineral markers (calcium, phosphate, parathyroid hormone, and vitamin D3). Statistical analyses are used to assess relationships between bone mineral biochemistry and factors like age, dialysis duration, and diabetes presence.Results: The study found a balanced gender distribution and median age consistent with global CKD trends. Hypertension was the most common CKD cause (48.6%). The prevalence of high turnover, low turnover, and mixed turnover is 54.95%, 23.42%, and 21.62%, respectively. Longer dialysis duration and absence of diabetes correlated with higher levels of calcium, iPTH, and ALP. Older patients showed significantly lower iPTH and ALP levels.Conclusions: CKD-MBD in chronic haemodialysis patients shows varied and complex patterns, highlighting the need for personalized treatment approaches.

Association between proteinuria and mineral metabolism disorders in chronic kidney disease: the Japan chronic kidney disease database extension (J-CKD-DB-Ex)

Chronic kidney disease-mineral and bone disorder (CKD-MBD) are recognized as a systemic disease affecting the prognosis of patients with CKD. Proper management of CKD-MBD is important to improve the prognosis of patients with CKD. Although proteinuria is recognized as a poor prognostic factor in these patients, few reports have examined its association with CKD-MBD. We examined the association between proteinuria and CKD-MBD using data from the Japan Chronic Kidney Disease Database Extension (J-CKD-DB-Ex). Among the patients registered in the J-CKD-DB-Ex, 30,977 with CKD stages G2–G5 who had serum creatinine, albumin, calcium, and phosphate concentrations measured at least once and urinalysis performed were included. The patients were divided into four groups (negative, 1+, 2+, and 3+) according to the degree of proteinuria. The association between proteinuria and CKD-MBD was examined by a logistic regression analysis. In a model adjusted for age, sex, diabetes, and the estimated glomerular filtration rate (eGFR), the odds ratio of the 3 + group compared with the negative group significantly increased to 2.67 (95% confidence interval, 2.29–3.13) for hyperphosphatemia, 2.68 (1.94–3.71) for hypocalcemia, and 1.56 (1.24–1.98) for hypomagnesemia. Proteinuria is associated with hyperphosphatemia, hypocalcemia, and hypomagnesemia in patients with CKD independently of eGFR.

Hemodialysis Patients May Benefit from Cholecalciferol Treatment Targeting High Level of 25(OH)D.

(1) Background and Objectives: Vitamin D is implicated in the pathogenesis of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) in hemodialysis (HD) patients, including the development of secondary hyperparathyroidism (SHP). While cholecalciferol supplementation is recommended for vitamin D deficiency correction, its impact on CKD-MBD remains inconsistent. The aim of this observational prospective study was to assess the effect of cholecalciferol in achieving high-normal serum 25-hydroxycholecalciferol (25(OH)D > 75 ng/mL) levels and its impact on CKD-MBD biochemical markers, including 1,25-dihydroxycholecalciferol (1,25(OH)2D) and parathormone (PTH) in HD patients. The study also evaluated the maintenance dosage required to sustain 25(OH)D levels within the 50-75 ng/mL range. (2) Materials and Methods: A total of 22 HD patients with baseline 25(OH)D levels 30-50 ng/mL received cholecalciferol (70,000 IU/week) to achieve the target serum 25(OH)D > 75 ng/mL. Baseline data on calcium, phosphate, 1-84 PTH, 25(OH)D, and 1,25(OH)2D serum levels were compared with the data when 25(OH)D > 75 ng/mL was targeted or when the highest 25(OH)D levels were noted. (3) Results: Cholecalciferol significantly improved vitamin D status in HD patients, with 73% reaching the target 25(OH)D level >75 ng/mL in a median time of 7.5 weeks, with a median total dose of 525,000 IU. This was associated with a significant rise in 1,25(OH)2D, decrease in 1-84 PTH, and no significant effect on calcium and phosphate levels. The median maintenance dose of cholecalciferol was established at 30,000 IU/week. (4) Conclusions: The findings support the use of cholecalciferol targeting high normal 25(OH)D levels to improve biochemical markers of CKD-MBD in HD patients.

General health and social outcomes 50 years after exposure to antenatal betamethasone: follow-up of a randomised controlled trial

BackgroundAntenatal corticosteroids are recommended for women at risk of preterm birth from 24 to 34 weeks’ gestation as they reduce neonatal morbidity and mortality, but evidence regarding their long-term effects on offspring is limited. This study assessed general health and social outcomes 50 years after antenatal exposure to corticosteroids.MethodsWe assessed 424 adult offspring of women who participated in the first randomised, double-blind, placebo-controlled trial of antenatal betamethasone for the prevention of neonatal respiratory distress syndrome. The first 717 mothers received two intramuscular injections of betamethasone (6 mg betamethasone sodium phosphate and 6 mg betamethasone acetate) or placebo given 24 h apart and the subsequent 398 received two injections of double dose betamethasone (12 mg betamethasone sodium phosphate and 12 mg betamethasone acetate) or equivalent volume of placebo. Follow-up included a health questionnaire and consent for access to administrative data sources. Outcome categories included mental health (depression, anxiety, bipolar affective disorder, schizophrenia and treatment or hospital admission for any mental health disorder), general health (chronic kidney disease, cancer diagnosis, bone fracture, oral health, allergies, functional difficulties and physical activity) and social outcomes (educational attainment, employment and criminal convictions). Investigators remained blinded to treatment allocation. Analyses were adjusted for gestational age at entry, sex and clustering.ResultsWe assessed 424 adult offspring (46% of survivors; mean [SD] age 49.3 [1.0] years; 212 [50%] female). There was no difference in mental health, general health and social outcomes between those exposed to betamethasone and those exposed to placebo, with the exception that osteoporotic site fracture in adulthood was more likely to have occurred in the betamethasone group compared with placebo (adjusted relative risk 1.57, 95% CI 1.00, 2.48, p = 0.05). No dose–effect relationship was evident and there was no difference in the proportion with at least one fracture. Follow-up rate and lack of in-person assessments were the main limitations.ConclusionsThere is no evidence that antenatal corticosteroids have clinically important effects on general health and social outcomes up to 50 years of age.

Zuogui Wan modulates macrophage polarization and promotes osteogenic differentiation through regulation of CD51-positive bone marrow mesenchymal stem cells

Background Zuogui Wan (ZGW) is a traditional herbal formula used to treat chronic kidney and bone diseases. Previous research has shown that ZGW slows down the aging process of bone marrow mesenchymal stem cells (BMSCs) and improves bone metabolism. However, its role in treating postmenopausal osteoporosis (PMOP) has not yet been fully investigated. Therefore, we investigated the therapeutic effects of ZGW and its potential mechanisms in an ovariectomy (OVX)-induced osteoporosis rat model. Results We observed significant improvements in bone loss and the osteoporotic phenotype in OVX rats treated with ZGW. These findings were confirmed with micro-computed tomography (micro-CT) and histomorphological analysis. We also discovered that ZGW reversed the macrophage imbalance, which in turn inhibited osteoclast differentiation and bone resorption. Furthermore, RNA-Seq results revealed the active expression of CD51 in BMSCs before and after ZGW therapy, which is associated with macrophage polarization and osteoblastic differentiation. The results also showed that ZGW decreased CD51 + BMSCs levels, which is closely related to the inhibition of osteoblast differentiation and promotion of osteoclast resorption. Conclusions Our study demonstrated that ZGW may improve postmenopausal osteoporosis by restoring macrophage polarization and down-regulating CD51 + BMSCs. In addition, ZGW promoted osteoblast formation and inhibited osteoclast resorption.

Intact Parathyroid Hormone (iPTH) Assay: An Early Approach for Bone Health Assessment in Chronic Renal Failure.

Chronic kidney disease (CKD) is a global public health burden with significantly increasing mortality. Chronic kidney disease leads to various complications, including anemia, cardiovascular complications, salt and water retention, metabolic acidosis, electrolyte disorders, and chronic kidney disease-mineral and bone disorder (CKD-MBD), amongst which CKD-MBD is a particularly important complication that develops early. In the present study, various biochemical analytes were assessed for their significance in monitoring the CKD-MBD in different stages of CKD. Only biochemistry markers were assessed in the present study, as X-rays and other radiological markers give positive results in the very late stages of CKD. The level of intact parathyroid hormone (iPTH) was raised or highly normal from the very early stages of chronic renal failure (CRF), and the differences in progressive stages were highly significant p<0.05. The correlation of iPTH with different biochemistry test parameters of CRF, such as creatinine, estimated glomerular filtration rate (eGFR), vitamin D, calcium, and inorganic phosphate, was also checked to determine its efficacy in the detection of CKD-MBD and, consequently, in preventing the complication of CKD. Parathyroid hormone (PTH) showed a significant positive correlation with creatinine in Stages 4 and 5 (p<0.05 in both stages). It was also observed that with the increase in the PTH level, there was a decrease in the estimated glomerular filtration rate in both Stage 4 and 5 patients. The level of iPTH was significantly increased from Stage 2 onwards; hence, it can be used as a diagnostic marker of CKD-MBD from the initial stages. Subsequent to diagnosis, the progression of CKD-MBD can be prevented by choosing the appropriate intervention from the wide array of treatment options available.

Ramadan fasting and exercise combination therapy: A novel approach for osteoporosis prevention in ovariectomized rats.

Osteoporosis is a chronic bone metabolic disease that affects millions of people worldwide, particularly the elderly and postmenopausal women. It is characterized by weakened bones, increasing the risk of fractures and leading to significant morbidity and mortality. The goal of the current study is to examine the reported osteo-preservative effects of exercise and/or fasting in the Ramadan fasting model (RFM) in ovariectomized (OVX) rats. The experimental intervention started 1month following the ovariectomy procedure and consisted of five 15-min exercise sessions per week at 18-25m/min and/or an approximately 13-h fast from sunrise to sunset (6:00 AM-19:00 PM). Serum bone metabolism biomarker levels were measured, and mineral concentrations in femoral ashed bones and digested serum were determined. Additionally, serum bone alkaline phosphatase (b-ALP), parathyroid hormone, osteocalcin, calcitonin, and vitamin D3 concentrations were measured using the competitive enzyme immunoassay technique. Calcium, magnesium, and phosphorus showed a notable decrease in mineral concentration among OVX rat femurs compared with the combination group (OVX + RFM + E) and control groups. In addition, homeostasis of serum concentrations of calcium, magnesium, and phosphorus was observed to increase in the OVX + RFM + E group rather than in the OVX group without intervention when compared with a control group. Furthermore, fasting and exercise, either alone or concurrently with ovariectomy, induced a non-significant elevation in osteocalcin, parathyroid hormone, and vitamin D3, whereas b-ALP and calcitonin increased significantly compared with those in control rats. The combination of the Ramadan fasting model and moderate intensity exercises among OVX rats manifested advantageous effects in bone biomarkers compared with OVX rats without intervention. This could be recommended as a lifestyle modification that is protective against osteoporosis, especially in the context of depleted estrogen hormone after menopause.

An Analysis of Cost Variation Among Drugs Available in the Indian Market for the Treatment of Chronic Bone-Related Ailments.

Treating widely prevalent bone illnesses such as back and neck pain, osteoarthritis, rheumatoid arthritis, gout, and osteoporosis with pharmacological medication can be excessively costly for both the individual and their family. This study aimed to conduct a cost minimization analysis by comparing the prices of Jan Aushadhi (JA) medications with the most expensive and least expensive branded alternatives available in India. The prices of the most costly, least costly branded, and JA medicines were acquired from the relevant websites. The cost difference, cost ratio, and percentage of cost variation were determined based on the guidelines outlined in the cost minimization analysis research. A total of 67 drugs/combinations used to treat various chronic bone ailments were analyzed. With regard to analgesic/anti-inflammatory drugs, the most expensive brand of diclofenac sodium + serratiopeptidase (50mg + 10mg) tablet was 32.5 times more expensive than the cheapest and 10.5 times more costly than the JA brand. Also, the paracetamol 325mg + tramadol 37.5mg combination of the branded tablets was more expensive than JA. Branded cyclosporine was 2.3 times more expensive than JA among immunosuppressants in the disease-modifying antirheumatic drugs (DMARD) group. The most expensive immunomodulator, leflunomide, costs four times more than JA. Hydrocortisone injection, an adjuvant, costs 10.8 times more than the cheapest and 2.1 times more than JA. IL-1 inhibitor + nutraceutical combination costs 4.8 times more than the costliest JA brand. Zoledronic acid was 16.1 and 6.8 times more expensive than the cheapest branded and JA drugs. Xanthine oxidase inhibitor febuxostat, used to treat gout, costs 5.2 and 3.3 times more than JA and the cheapest brands. This cost minimization study, the first to the best of our knowledge in the field of chronic musculoskeletal ailments, indicates the usefulness of JA drugs in reducing the patient's financial costs for most drugs.

Phosphorous metabolism and manipulation in chronic kidney disease.

Chronic kidney disease-mineral bone disorder (CKD-MBD) is a syndrome commonly observed in subjects with impaired renal function. Phosphate metabolism has been implicated in the pathogenesis of CKD-MBD and according to the phosphorocentric hypothesis may be the key player in the pathogenesis of these abnormalities. As phosphorous is an essential component for life, absorption from the bowel, accumulation and release from the bones, and elimination through the kidneys are all homeostatic mechanisms that maintain phosphate balance through very sophisticated feedback mechanisms, which comprise as main actors: vitamin D (VD), parathyroid hormone (PTH), calciproteins particles (CPPs), fibroblast growth factor-23 (FGF-23) and other phosphatonins and klotho. Indeed, as the renal function declines, factors such as FGF-23 and PTH prevent phosphate accumulation and hyperphosphatemia. However, these factors per se may be responsible for the organ damages associated with CKD-MBD, such as bone osteodystrophy and vascular calcification. We herein review the current understanding of the CKD-MBD focusing on phosphorous metabolism and the impact of phosphate manipulation on surrogate and hard outcomes.

Efficacy and safety of sucroferric oxyhydroxide versus sevelamer carbonate: A systematic review and meta-analysis.

Phosphate binders are commonly used in patients receiving kidney replacement therapy (KRT), aiming to reduce and maintain serum phosphorus. Chronic kidney disease-mineral and bone disorder has been linked to reduced lifespan and worsened quality of life. This study aims to examine the efficacy and safety of sucroferric oxyhydroxide versus sevelamer carbonate in patients receiving KRT. The data sources examined were MEDLINE (PubMed), Scopus, and the Cochrane Central Register of Controlled Clinical Trials with a search deadline of October 2023. We examined randomized controlled trials that compared sucroferric oxyhydroxide versus sevelamer carbonate in the adult population receiving KRT. We performed a meta-analysis combining the data from trials, using R-studio. Inclusion criteria were met by five randomized trials. There was no statistically significant difference in the reduction of serum phosphorus between the two groups (MD: -0.07 mmol/L, 95% CI-random effects: -0.15 to 0.02). In the same line, a non-statistically significant difference was observed in serum i-PTH reduction between the two drugs (MD = -1.53 mg/dL, 95% CI = (-4.45, 1.4), p = 0.26, random effects model). No statistically significant difference was observed in all adverse events between the two groups (odds ratio: 1.11, 95% CI: 0.65-1.88, random effects model). Further analysis of gastrointestinal adverse events revealed that sevelamer carbonate increases gastrointestinal adverse events by up to 60% (odds ratio: 1.60, 95% CI: 1.31-1.97, common (fixed) effect model). This meta-analysis of randomized trials showed that both drugs, sucroferric oxyhydroxide and sevelamer equally and effectively controlled serum phosphorus levels, whereas sucroferric oxyhydroxide revealed a better profile in terms of gastrointestinal adverse events. Sucroferric oxyhydroxide is a valuable option for patients receiving KRT when sevelamer carbonate is more difficult to tolerate.

Modulation of NRF2/KEAP1 Signaling by Phytotherapeutics in Periodontitis.

Periodontitis affects up to 40% of adults over 60 years old and is a consequence of gingivitis. Periodontitis is characterized by a chronic inflammation, periodontal damage, and alveolar bone resorption. The nuclear factor erythroid 2-related factor 2 (NFE2L2 or NRF2)/Kelch-like ECH-Associated Protein 1 (KEAP1) (NRF2/KEAP1) signaling pathway plays a key role in periodontitis by modulating redox balance and inflammation of the periodontium. However, NRF2 expression is decreased in gingival tissues of patients with periodontitis while oxidative stress is significantly increased in this pathology. Oxidative stress and lipopolysaccharide (LPS) produced by gram-negative bacteria favor the production of inflammatory causing periodontal inflammation and favoring alveolar bone. In this review, we analyzed the current literature regarding the role of natural and synthetic compounds in modulating the NRF2/KEAP1 pathway in in vitro and in vivo models of periodontitis in order to evaluate new potential treatments of periodontitis that can improve the outcome of this disease.

Puerarin alleviates osteoporosis in rats by targeting the JAK2/STAT3 signaling pathway.

Osteoporosis (OP) is a common chronic progressive bone disease that increases fracture risk in postmenopausal women. Research suggests that puerarin (Pue) may be an effective treatment for OP. This study examined the effects and underlying mechanisms of Pue in treating postmenopausal osteoporosis (PMOP) in rats. Sprague-Dawley (SD) rats underwent bilateral ovariectomy to simulate PMOP and were then treated with subcutaneous injections of Pue. Bone mineral density (BMD) was measured using a bone densitometer. Micro-CT scans assessed femur bone structure and various parameters were calculated: bone volume fraction (BV/TV), bone surface density (BS/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular separation (Tb.Sp), and bone surface area-to-bone volume ratio (BS/BV). Hematoxylin-eosin (HE) staining was employed to observe femoral tissue pathology. Serum levels of bone formation metabolism-related markers-osteocalcin (OC), bone alkaline phosphatase (BALP), and procollagen type I N-terminal propeptide (PINP)-were measured via enzyme-linked immunosorbent assay (ELISA). The protein expression levels of the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway in bone tissue were evaluated using Western blotting assay. The results showed improved bone density and reduced bone loss in rats treated with Pue. There were also significant increases in serum levels of OC and BALP, indicating enhanced osteogenesis. Furthermore, there was a decrease in activation of the JAK2/STAT3 pathway in femoral tissue, suggesting a pathway inhibition. These findings indicate that Pue may combat osteoporosis by promoting osteogenesis and inhibiting activation of the JAK2/STAT3 pathway activation.

Adiposity and Mineral Balance in Chronic Kidney Disease.

Bone homeostasis is balanced between formation and resorption activities and remain in relative equilibrium. Under disease states this process is disrupted, favoring more resorption over formation, leading to significant bone loss and fracture incidence. This aspect is a hallmark for patients with chronic kidney disease mineral and bone disorder (CKD-MBD) affecting a significant portion of the population, both in the United States and worldwide. Further study into the underlying effects of the uremic microenvironment within bone during CKD-MBD are critical as fracture incidence in this patient population not only leads to increased morbidity, but also increased mortality. Lack of bone homeostasis also leads to mineral imbalance contributing to cardiovascular calcifications. One area understudied is the possible involvement of bone marrow adipose tissue (BMAT) during the progression of CKD-MBD. BMAT accumulation is found during aging and in several disease states, some of which overlap as CKD etiologies. Importantly, research has found presence of BMAT inversely correlates with bone density and volume. Understanding the underlying molecular mechanisms for BMAT formation and accumulation during CKD-MBD may offer a potential therapeutic avenue to improve bone homeostasis and ultimately mineral metabolism.

Diagnostic imaging findings in lame Warmblood horses with bone injuries of the medial proximal phalanx glenoid cavity.

This retrospective study aims to describe baseline and follow-up imaging findings in subchondral and trabecular bone damage occurring outside of the sagittal groove in the proximal phalanx (P1) glenoid in a case series of lame Warmblood horses. Thirteen lame horses (16 forelimbs) with standing magnetic resonance imaging (sMRI) evidence of nonsagittal groove glenoid subchondral and trabecular bone injury of P1 as the main lesion were included. All injuries were located at the medial aspect of the P1 glenoid. At sMRI, changes included subchondral bone plate thickening and trabecular sclerosis, bone marrow edema-like signal, subchondral bone resorption (11/16), and new bone production (8/16). Subchondral bone resorption in the transverse plane was linear (8/11), round (2/11), or ill-defined (1/11). Sclerosis, bone resorption, and new bone production were seen radiographically in 10, 4, and 5 limbs, respectively. All limbs had concurrent metacarpal condyle sMRI imaging abnormalities, osteophytosis, and joint effusion. Follow-up sMRIs were obtained in 8 of 16 limbs, five of which showing progression of the resorptive lesion. One horse encountered a comminuted fracture of the affected P1 18 months after the follow-up sMRI examination. The imaging appearance of the medial glenoid bone injuries of P1 in this case series is consistent with chronic bone overload. The linear configuration of bone resorption seen in eight lesions suggests short, incomplete stress fractures, which is supported by the ultimate catastrophic fracture occurring in one case.

12324 Clinical Features And PHEX Variants Of Adults With X-Linked Hypophosphatemia

Abstract Disclosure: L.P. Valadares: None. D.R. Carvalho: None. F.S. Lopes: None. R.S. Oliveira: None. L.G. Castro: None. X-linked hypophosphatemia (XLH), caused by loss-of-function PHEX mutations, is a lifelong renal phosphate-wasting disorder and the main cause of inherited hypophosphatemia. In adults, chronic hypophosphatemia leads to impaired bone mineralization and persistent osteomalacia. Short stature, lower limb deformities and musculoskeletal chronic pain can significantly impact the daily lives of affected individuals. This study aimed to describe the clinical and molecular profiles of 23 adults with genetically proven XLH who are being followed at a tertiary medical center in Brazil. We conducted a retrospective analysis of their medical records. The median age at diagnosis was 3.0 years (IQR 2.0-8.0) and the mean age at first visit at the adult care unit was 30.5 years (±12.7). Their mean final height was 144.2 cm (±10.5), with a mean body mass index (BMI) of 28.1 kg/m2 (±4.9). Nine patients were overweight, and seven were obese. Sixteen patients had a positive family history of rickets, and nine had offspring with XLH. Among the 14 different PHEX mutations that were identified, six had not been previously reported. Hypophosphatemia was observed in 21 patients at presentation at the adult care unit, increased serum alkaline phosphatase levels in 19, and 12 showed increased PTH levels. Chronic bone and muscular pain were reported by sixteen patients, eighteen had lower limb deformities, and six had a history of fractures and/or pseudofractures. Seventeen patients underwent orthopedic surgeries, with an average of 3.8 surgical interventions per patient. Nephrolithiasis and/or nephrocalcinosis were observed in nine patients, but none had glomerular filtration rate below 60 mL/min adjusted to 1.73 m2 of body surface. Three patients were on conventional treatment (phosphate and calcitriol) upon presentation at the adult care unit, five patients had never received XLH-specific treatment, and fifteen discontinued conventional therapy after completing skeletal growth, with a mean therapy duration of 12.1 years (±3.5). Out of the 20 patients without treatment, 16 were initiated on pharmacological therapy based on symptoms and signs of persistent osteomalacia. Eleven started combined phosphate and calcitriol supplementation, while five received calcitriol monotherapy. This cohort underscores that adults with XLH experience significant musculoskeletal morbidity throughout their lives, and require long-term follow-up, including assessment of energy metabolism. Importantly, most of them benefits from maintaining pharmacological treatment in adulthood. Presentation: 6/2/2024

A-038 Interlaboratory Comparison of Parathyroid Hormone Analytical Results Across Clinical Assays from 8 Manufacturers - Steps Towards Standardization

Abstract Background Parathyroid hormone (PTH) is an 84 amino acid peptide produced by the parathyroid gland and is a key biomarker used for the diagnosis and treatment of Chronic Kidney Disease-Mineral and Bone Disorder, as well as hypo- and hyperparathyroidism. PTH clinical assays were previously reported to exhibit significant inter-assay measurement variability, which limits the utility of PTH as a diagnostic biomarker and can result in the misclassification of patients. Thus, there is a need for PTH clinical assay standardization to improve clinical assay measurement agreement. The Centers for Disease Control and Prevention’s Clinical Standardization Program (CDC-CSP) will launch a PTH standardization program, which is in support of and coordinated with the IFCC Committee on Bone Metabolism. In preparation, the CDC-CSP conducted an Inter-Laboratory Comparison Study to evaluate the current status of PTH inter-assay variability and to investigate potential sources of variability. Methods Eight PTH assay manufacturer’s laboratories measured PTH in 42 deidentified, fresh-frozen single donor serum samples in duplicate over 2 independent runs. Sample PTH concentrations ranged from 1.3 - 324 pg/mL, based on initial screening values. Five manufacturers submitted data for 2 different assays, resulting in PTH measurements from 13 assays total. Data were submitted to the CDC CSP for analysis. Results Assay precision was &amp;lt;5% for 10/13 measurement procedures (MP) assessed and 3 MPs exhibited precisions between 5 - 18%. Assay-specific PTH measurements demonstrated good linear correlation compared to the all-assay mean concentration. Interestingly, inter-assay variability increased with increasing PTH concentrations, with individual sample standard deviations increasing from 2.9 - 123, with a mean SD of 24.1 and individual sample CVs increasing from 18.9 - 44.5%, with a mean CV of 24.2%. Conclusions This study provides new insights into PTH inter-assay variability and assay performance for assays commonly used in the clinical setting. The findings of this PTH Interlaboratory Comparison Study establish a baseline for PTH inter-assay variability and will guide future PTH standardization efforts.

Hemoglobin α-derived peptides VD-hemopressin (α) and RVD-hemopressin (α) are involved in electroacupuncture inhibition of chronic pain.

Knee osteoarthritis (KOA) is a chronic degenerative bone metabolic disease that primarily affects older adults, leading to chronic pain and disability that affect patients' daily activities. Electroacupuncture (EA) is a commonly used method for the treatment of chronic pain in clinical practice. Previous studies indicate that the endocannabinoid system is involved in EA analgesia, but whether endocannabinopeptide VD-hemopressin (α) and RVD-hemopressin (α) derived from hemoglobin chains are involved in EA analgesia is unclear. RNA-seq technology was used to screen which genes involved in EA analgesia. The expression of hemoglobin α chain and 26S proteasome were determined by Western blotting. The level of VD-hemopressin (α) and RVD-hemopressin (α) were measured by UPLC-MS/MS. Microinjection VD-Hemopressin (α), RVD-Hemopressin (α) and 26S proteasome inhibitor MG-132 into vlPAG, then observe mechanical and thermal pain thresholds. Therefore, we used RNA-seq to obtain differentially expressed genes Hba-a1 and Hba-a2 involved in EA analgesia in the periaqueductal gray (PAG), which were translated into the hemoglobin α chain. EA significantly increased the expression of the hemoglobin α chain and the level of hemopressin (α) and RVD-hemopressin (α). Microinjection of VD-hemopressin (α) and RVD-hemopressin (α) into the ventrolateral periaqueductal gray (vlPAG) mimicked the analgesic effect of EA, while CB1 receptor antagonist AM251 reversed this effect. EA significantly increased the expression of 26S proteasome in KOA mice. Microinjection of 26S proteasome inhibitor MG132 before EA prevented both the anti-allodynic effect and upregulation of the concentration of RVD-hemopressin (α) by EA treatment and upregulated the expression of the hemoglobin α chain. Our data suggest that EA upregulated the concentration of VD-hemopressin (α) and RVD-hemopressin (α) through enhancement of the hemoglobin α chain degradation by 26S proteasome in the PAG, then activated the CB1 receptor, thereby exerting inhibition of chronic pain in a mouse model of KOA. These results provide new insights into the EA analgesic mechanisms and reveal possible targets for EA treatment of chronic pain.