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Clinical Kidney Journal Jun 2024This study investigated whether parathyroid hormone (PTH) lowering with etelcalcetide, and the consequent effects on mineral and bone metabolism, could improve serum...
BACKGROUND
This study investigated whether parathyroid hormone (PTH) lowering with etelcalcetide, and the consequent effects on mineral and bone metabolism, could improve serum calcification propensity (T50 time) and decrease calciprotein particle (CPP) load in hemodialysis patients with secondary hyperparathyroidism.
METHODS
In this single-arm, prospective, dose-escalation proof-of-principle study, hemodialysis patients received etelcalcetide at 2.5 mg/dialysis session with increments of 2.5 mg every 4 weeks to a maximum dose of 15 mg three times a week or until a pre-specified safety endpoint was reached, followed by an 8-week wash-out phase.
RESULTS
Out of 36 patients recruited (81% male, 62 ± 13 years), 16 patients completed the study per protocol with a mean maximum tolerated dose of etelcalcetide of 9.5 ± 2.9 mg/dialysis session. With escalating doses of etelcalcetide, PTH and serum calcium levels significantly decreased (< 0.0001). While there was no significant change in T50 times or serum phosphate levels, etelcalcetide did yield significant and consistent reductions in serum levels of endogenous calciprotein monomers [-35.4 (-44.4 to -26.5)%, < 0.0001], primary [-22.4 (-34.5 to -10.3)%, < 0.01] and secondary CPP [-29.1 (-45.7 to -12.4)%, < 0.01], an effect that was reversed after therapy withdrawal. Serum levels of osteoclastic markers significantly decreased with escalating doses of etelcalcetide, while levels of the osteoblastic marker remained stable.
CONCLUSIONS
Lowering of PTH with etelcalcetide did not result in statistically significant changes in T50. By contrast, homogenous reductions in serum levels of calciprotein monomers, primary and secondary CPP were observed.
PubMed: 38919277
DOI: 10.1093/ckj/sfae097 -
Minerva Surgery Jun 2024Primary hyperparathyroidism is characterized by elevated plasma calcium levels due to inappropriate secretion of parathyroid hormone (PTH) in most cases by an...
BACKGROUND
Primary hyperparathyroidism is characterized by elevated plasma calcium levels due to inappropriate secretion of parathyroid hormone (PTH) in most cases by an adenomatous or hyperplastic parathyroid. We present a retrospective analysis of a large cohort of patients operated on of parathyroidectomy in our center analyzing their diagnostic characteristics, intraoperative match and surgical outcomes.
METHODS
We included patients with benign parathyroid disease who underwent parathyroidectomy associated or not with hemi- or total thyroidectomy at the Sant'Anna University Hospital of Ferrara between September 2003 and September 2022.
RESULTS
In our study 371 patients fulfilled the inclusion criteria. The most widely used preoperative imaging method was ultrasound, followed by 99mTc-sestamibi scintigraphy. In most cases, preoperative imaging correctly localized the affected parathyroid. Considering the intraoperative site of the pathologically affected parathyroid, the majority of pathological parathyroids were located in the lower districts of the neck and a smaller percentage in the upper, intermediate, and ectopic sites. Postoperative complications were infrequent.
CONCLUSIONS
The main challenge in parathyroid surgery lies in the difficulty in localizing the pathological parathyroid at the surgical site, which can lengthen the surgical time by increasing comorbidities. Currently, the results on pathological parathyroid localization are good. Technology needs to be developed toward greater diagnostic accuracy and minimally invasive surgical approaches.
PubMed: 38916537
DOI: 10.23736/S2724-5691.24.10285-7 -
Reumatismo Jun 2024Fragility fractures (FF) resulting from osteoporosis pose a significant public health challenge in Italy, with considerable socio-health and economic implications....
OBJECTIVE
Fragility fractures (FF) resulting from osteoporosis pose a significant public health challenge in Italy, with considerable socio-health and economic implications. Despite the availability of safe and effective drugs, osteoporosis remains underdiagnosed and undertreated, leaving over 2 million high-risk Italian women without treatment. This paper aims to identify and propose key improvements in the management of osteoporosis, focusing particularly on the critical issues related to the use of anabolic drugs in secondary prevention, according to the current Italian Medicines Agency (AIFA) Note 79.
METHODS
The Expert Panel, composed of nine recognized Italian experts in rheumatology, analyzed current practices, prescribing criteria, and the most recent literature. Three main reasons for revising the indications on pharmacological treatment of osteoporosis were identified: inadequate treatment of osteoporosis, new evidence regarding frontline placement of anabolics in high-risk conditions, and emerging sequential or combined strategies.
RESULTS
The proposed improvements include the adoption of the Derived Fracture Risk Assessment algorithm for accurate fracture risk assessment, revision of AIFA Note 79 to reflect current evidence, improved prescribing appropriateness, broader access to anabolic agents, and the provision of sequential therapies with antiresorptives for teriparatide. These changes aim to enhance patient outcomes, streamline healthcare processes, and address the high percentage of undertreated individuals.
CONCLUSIONS
This expert opinion emphasizes the importance of the appropriate use of anabolic drugs to reduce FF and associated costs while ensuring the sustainability of the National Health Service. The proposed recommendations are in line with the latest scientific evidence, providing a comprehensive strategy to optimize the management of osteoporosis in Italy. On behalf of the Study Group on Osteoporosis and Skeletal Metabolic Diseases of the Italian Society of Rheumatology.
Topics: Humans; Italy; Anabolic Agents; Osteoporosis; Bone Density Conservation Agents; Osteoporotic Fractures; Female; Teriparatide; Risk Assessment; Secondary Prevention; Expert Testimony
PubMed: 38916162
DOI: 10.4081/reumatismo.2024.1696 -
Journal of Nephrology Jun 2024Mortality in hemodialysis (HD) patients remains unacceptably high compared with that of the general population and despite the continuous improvement of dialysis...
BACKGROUND
Mortality in hemodialysis (HD) patients remains unacceptably high compared with that of the general population and despite the continuous improvement of dialysis techniques. This study aimed to assess the role of alkaline phosphatase serum levels on cardiovascular and overall mortality in the RISCAVID study cohort through a long follow-up period, looking for associations with known risk factors for poor outcome.
METHODS
In June 2004, a prospective observational study was started focusing on the cardiovascular risk in hemodialysis patients who lived in the north-west area of Tuscany (RISCAVID, "RISchio CArdiovascolare nei pazienti afferenti all'Area Vasta In Dialisi"). The RISCAVID cohort included 572 prevalent patients on maintenance HD for at least three months. Morbid or fatal events were prospectively recorded at 6-month intervals for a follow up time of 216 months.
RESULTS
In univariable Cox regression analysis, dialysis technique, Geriatric Nutritional Risk Index, peripheral vascular disease, and intact parathyroid hormone and total calcium serum levels were significantly associated with baseline alkaline phosphatase serum levels. Cox multivariable analysis showed that elevated serum alkaline phosphatase levels (the highest quartile), advanced age, dialysis vintage, type of vascular access, Geriatric Nutritional Risk Index, C-reactive protein and calcium serum levels, history of cardiovascular disease and peripheral vascular disease were independent predictors of overall mortality in maintenance HD patients. The fourth quartile of alkaline phosphatase was associated with all-cause 10-year mortality (HR: 1.47; 95% CI: 1.177-1.834) with a 47% increase with respect to the 1st, 2nd, and 3rd quartiles. This was also observed for 18-year all-cause mortality.
CONCLUSIONS
Adjusted proportional analysis showed the alkaline phosphatase value to be an independent and powerful predictor of overall mortality in the hemodialysis population.
PubMed: 38913269
DOI: 10.1007/s40620-024-01956-1 -
Frontiers in Immunology 2024Bone regeneration is a complex pathophysiological process determined by molecular, cellular, and biomechanical factors, including immune cells and growth factors.... (Review)
Review
Bone regeneration is a complex pathophysiological process determined by molecular, cellular, and biomechanical factors, including immune cells and growth factors. Fracture healing usually takes several weeks to months, during which patients are frequently immobilized and unable to work. As immobilization is associated with negative health and socioeconomic effects, it would be desirable if fracture healing could be accelerated and the healing time shortened. However, interventions for this purpose are not yet part of current clinical treatment guidelines, and there has never been a comprehensive review specifically on this topic. Therefore, this narrative review provides an overview of the available clinical evidence on methods that accelerate fracture healing, with a focus on clinical applicability in healthy patients without bone disease. The most promising methods identified are the application of axial micromovement, electromagnetic stimulation with electromagnetic fields and direct electric currents, as well as the administration of growth factors and parathyroid hormone. Some interventions have been shown to reduce the healing time by up to 20 to 30%, potentially equivalent to several weeks. As a combination of methods could decrease the healing time even further than one method alone, especially if their mechanisms of action differ, clinical studies in human patients are needed to assess the individual and combined effects on healing progress. Studies are also necessary to determine the ideal settings for the interventions, i.e., optimal frequencies, intensities, and exposure times throughout the separate healing phases. More clinical research is also desirable to create an evidence base for clinical guidelines. To make it easier to conduct these investigations, the development of new methods that allow better quantification of fracture-healing progress and speed in human patients is needed.
Topics: Humans; Fracture Healing; Animals; Fractures, Bone; Bone Regeneration; Magnetic Field Therapy
PubMed: 38911851
DOI: 10.3389/fimmu.2024.1384783 -
Indian Journal of Endocrinology and... 2024We aimed to describe the clinical, biochemical and etiological profile of patients referred with a provisional diagnosis of rickets in tertiary care centres. In...
INTRODUCTION
We aimed to describe the clinical, biochemical and etiological profile of patients referred with a provisional diagnosis of rickets in tertiary care centres. In addition, we tried to propose a diagnostic algorithm for the evaluation of such patients.
METHODS
This was a retrospective cross-sectional study conducted in two tertiary care centres of West Bengal. Data of patients were retrieved between 2014 and 2021.
RESULTS
Out of 101 children, 22 had conditions simulating rickets. Renal tubular acidosis (RTA) was the most common (53.2%) etiology of rickets, followed by phosphopenic rickets (PR) (22.8%) and calcipenic rickets (CR) (17.7%). The prevalence of true nutritional rickets (NR) was only 8.9%. Children with RTA had a significantly higher prevalence of chronic ill health (69%) and polyuria (95.2%). Weight standard deviation score (SDS) and body mass index (BMI) SDS scores were significantly lower in the RTA group compared to others. Around 90.5% of children with RTA, and none in the other groups, had hypokalemia. Biochemically, hypophosphatemia and elevated alkaline phosphatase (ALP) were present in all patients with PR and CR. Compared to CR, median serum phosphate was significantly lower in the PR group. A significant difference in ALP values was noticed in patients with hypophosphatemia (815 ± 627 IU/L) compared to those without (279 ± 204 IU/L). Plasma parathyroid hormone (PTH) of 100 pg/ml seemed useful to differentiate CR from other forms.
CONCLUSION
NR is uncommon in tertiary care centres. Children with rickets should be approached systematically with the estimation of ALP, phosphorus, creatinine, calcium, PTH and 25-hydroxy vitamin D to reach an etiological diagnosis.
PubMed: 38911108
DOI: 10.4103/ijem.ijem_221_23 -
Journal of Orthopaedic Case Reports Jun 2024Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage degradation, bone remodeling, and pain. Recent evidence suggests that Vitamin D...
INTRODUCTION
Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage degradation, bone remodeling, and pain. Recent evidence suggests that Vitamin D insufficiency, alterations in parathyroid hormone (PTH) levels, and dyslipidemia may play roles in the pathophysiology of OA, affecting calcium homeostasis and bone health. We investigated the association between Vitamin D, PTH levels, lipid profile, and calcium homeostasis in OA patients.
MATERIALS AND METHODS
This case-control study involved 200 participants, divided into OA and control groups, at a tertiary care center from April to May 2023. Serum levels of 25-hydroxyvitamin D, PTH, total cholesterol, HDL, LDL, triglycerides, and calcium were measured. Statistical analysis was conducted to assess correlations between these biomarkers and OA status.
RESULTS
OA patients demonstrated significantly lower Vitamin D levels and higher PTH and total cholesterol levels compared to controls. Vitamin D insufficiency was prevalent, with a notable correlation between decreased Vitamin D levels, elevated PTH, and dyslipidemia. These findings suggest a potential metabolic interplay affecting OA progression and symptomatology.
CONCLUSION
The study highlights a significant association between Vitamin D insufficiency, altered PTH levels, and lipid dysregulation in OA patients, underscoring the importance of assessing these parameters in the clinical management of OA. Further research is needed to explore the therapeutic implications of correcting Vitamin D insufficiency and lipid abnormalities in OA.
PubMed: 38910978
DOI: 10.13107/jocr.2024.v14.i06.4544 -
Cureus May 2024Introduction Primary hyperparathyroidism (PHPT) has undergone a considerable change from being symptomatic to asymptomatic. This is the first large study from North...
Introduction Primary hyperparathyroidism (PHPT) has undergone a considerable change from being symptomatic to asymptomatic. This is the first large study from North India to study the clinical and biochemical features and surgical outcomes in the present era. Study design This is a cross-sectional study that was conducted in the Department of Endocrinology (SKIMS) from February 2021 to December 2022, in which 103 patients diagnosed with PHPT were included. Evaluation included measurement of total calcium, phosphorus, alkaline phosphate, intact parathyroid hormone, 25-hydroxy vitamin, 24-hour urinary calcium, radiological survey of hands and skull, Dual Energy X-ray absorptiometry, and ultrasonography (USG) of the abdomen. USG neck and technetium-99m sestamibi scans were used for preoperative localization; however, in cases of discordance between these investigations or suspicions of multi-glandular disease, four-dimensional computerized tomography of the neck was used. Patients were subjected to surgery according to the guidelines and monitored post-surgery for complications like hypocalcemia and hungry bone syndrome and to document the cure. Results The mean age of patients was 42.8±14.73 years, with a female-to-male ratio of 4.4:1. The mean eGFR of patients was 99.1±30.87 ml/min, with 55 (53.4%) of them having renal disease. Osteoporosis and fractures were present in 41 (39.8%) and 5 (4.8%) patients, respectively. Cholelithiasis and pancreatitis were present in 25 (24.3%) and 5 (4.9%) patients, respectively. Hypertension (HTN) and diabetes mellitus (DM) were the commonest comorbidities, which were present in 34 (33.1%) and 15 (14.5%) patients, respectively. Mean preoperative levels of calcium, phosphorus (PO4), alkaline phosphate (ALP), intact parathyroid hormone (iPTH), 25(OH)vitamin D, and 24-hour urinary calcium were 12.1 mg/dl, 2.35 mg/dl, 210.2 U/L, 332.9 pg/ml, 25.7 ng/ml, and 452.1 mg/day, respectively. The most common type was right inferior parathyroid adenoma, present in 45 cases (43.7%), followed by left inferior parathyroid adenoma in 31 cases (30.1%). A total of 75 patients (72.8%) underwent minimally invasive parathyroidectomy, with 68 patients (90.7%) achieving a biochemical cure. The mean adenoma weight was 3.19±2.25 g. There was no statistically significant correlation (r) between preoperative biochemical parameters and adenoma weight. Conclusion Despite improvements in imaging and the easy availability of immunoassays for early diagnosis, renal disease continued to be the most common presentation, followed by skeletal involvement in our population. In developing countries like India, any patient presenting with nephrolithiasis or nephrocalcinosis, low bone mass, or fragility fractures should be evaluated for PHPT.
PubMed: 38910736
DOI: 10.7759/cureus.60965 -
Journal of Theoretical Biology Jun 2024Treating bone-cartilage defects is a fundamental clinical problem. The ability of damaged cartilage to self-repair is limited due to its avascularity. Left untreated,...
Treating bone-cartilage defects is a fundamental clinical problem. The ability of damaged cartilage to self-repair is limited due to its avascularity. Left untreated, these defects can lead to osteoarthritis. Details of osteochondral defect repair are elusive, but animal models indicate healing occurs via an endochondral ossification-like process, similar to that in the growth plate. In the growth plate, the signalling molecules parathyroid hormone-related protein (PTHrP) and Indian Hedgehog (Ihh) form a feedback loop regulating chondrocyte hypertrophy, with Ihh inducing and PTHrP suppressing hypertrophy. To better understand this repair process and to explore the regulatory role of signalling molecules on the regeneration process, we formulate a reaction-diffusion mathematical model of osteochondral defect regeneration after chondrocyte implantation. The drivers of healing are assumed to be chondrocytes and osteoblasts, and their interaction via signalling molecules. We model cell proliferation, migration and chondrocyte hypertrophy, and matrix production and conversion, spatially and temporally. We further model nutrient and signalling molecule diffusion and their interaction with the cells. We consider the PTHrP-Ihh feedback loop as the backbone mechanisms but the model is flexible to incorporate extra signalling mechanisms if needed. Our mathematical model is able to represent repair of osteochondral defects, starting with cartilage formation throughout the defect. This is followed by chondrocyte hypertrophy, matrix calcification and bone formation deep inside the defect, while cartilage at the surface is maintained and eventually separated from the deeper bone by a thin layer of calcified cartilage. The complete process requires around 48 months. A key highlight of the model demonstrates that the PTHrP-Ihh loop alone is insufficient and an extra mechanism is required to initiate chondrocyte hypertrophy, represented by a critical cartilage density. A parameter sensitivity study reveals that the timing of the repair process crucially depends on parameters, such as the critical cartilage density, and those describing the actions of PTHrP to suppress hypertrophy, such as its diffusion coefficient, threshold concentration and degradation rate.
PubMed: 38908475
DOI: 10.1016/j.jtbi.2024.111874 -
Langenbeck's Archives of Surgery Jun 2024Over recent years, various advanced minimally invasive techniques have been developed for parathyroidectomy, and there was a universal acceptance of these less invasive... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
BACKGROUND
Over recent years, various advanced minimally invasive techniques have been developed for parathyroidectomy, and there was a universal acceptance of these less invasive procedures by surgeons. This study is designed to compare overall outcomes between endoscopic versus focused, single gland parathyroidectomy using intraoperative rapid parathyroid hormone (ioPTH) changes under general anesthesia in primary hyperparathyroidism (PHPT) patients.
METHOD
In this randomized clinical trial, 96 patients diagnosed with PHPT were randomly assigned into two groups endoscopic and focused parathyroidectomy. Baseline clinical and demographical data were collected along with perioperative features. The success rate was evaluated based on ioPTH changes.
RESULTS
The ioPTH levels after five minutes in the endoscopic group were significantly lower than the focused group (P = 0.005). The success rate for endoscopic and the focused method was 95.3% and 77.1% during the first five minutes (P = 0.013) and 100% in both groups after ten minutes. A decrease in parathyroid hormone levels was significant in each group but not between each other. Postoperative calcium levels were significantly lower in the focused method (P = 0.042). The focused group also had a significantly shorter operation time than the endoscopic group (P < 0.001). Patient satisfaction with cosmetic outcome was significantly higher in the endoscopic group compared to the focused group.
CONCLUSION
The endoscopic technique was superior to the unilateral focused neck exploration parathyroidectomy in the management of single-gland PHPT. Influencing aspects included higher postoperative calcium levels, more rapid success achievement, and satisfactory cosmetic outcomes in the endoscopic group. However, patient selection and accurate adenoma localization are vital in this method.
Topics: Humans; Parathyroidectomy; Hyperparathyroidism, Primary; Male; Female; Middle Aged; Endoscopy; Treatment Outcome; Adult; Parathyroid Hormone; Aged; Operative Time
PubMed: 38907761
DOI: 10.1007/s00423-024-03390-0