Journal of Bone and Mineral Metabolism最新文献

Introduction: Romosozumab is an anti-sclerostin antibody drug with potent bone formation-promoting and bone resorption-inhibiting properties. It enhances bone mineral density and has a novel effect in preventing fractures. However, there have been reports of non-responders to romosozumab.

Findings: If the least significant change is defined as 3%, only 2-12% of patients with spine osteoporosis are non-responders, and romosozumab is highly effective in this population. Low-type 1 amino-terminal propeptide (P1NP) levels during the early treatment phase are associated with non-responders early in treatment. The researchers found a cutoff value of 50.3 μg/L of P1NP in the first month of treatment. In contrast, hip osteoporosis does not respond (54-57% of the time). Low P1NP levels at the start of treatment increase the risk of non-responders. The cutoff value for P1NP was reported as 53.7 μg/L at the beginning of treatment. However, failure to meet these cutoff values does not necessarily indicate that the patient is a non-responder and does not justify a change in drug administration.

Conclusions: In spine osteoporosis, romosozumab demonstrates high effectiveness, with approximately 2-12% of patients showing no response. However, in hip osteoporosis, approximately 54-57% do not respond to the treatment with romosozumab.

Introduction: Previous research has demonstrated that even minor changes in thyroid function are associated with an increased risk of osteoporosis (OP). However, the causal relationship between thyroid disorders and the development of OP remains unclear. To address this, we aim to investigate the connection between genetic predispositions to various thyroid disorders and OP using a two-sample Mendelian randomization (MR) approach.

Materials and methods: Instrumental variables (IVs) for multiple thyroid disorders were sourced from a large genome-wide association study (GWAS) meta-analysis dataset. Summary-level data for OP were obtained from the FinnGen consortium. Inverse variance weighting (IVW) methods served as the primary approach for MR analysis. Sensitivity analyses included MR-Egger regression, heterogeneity testing, multiple validity tests, and leaFve-one-out sensitivity tests.

Results: IVW analysis revealed a direct causal effect of hypothyroidism (OR = 1.105, 95% CI 1.023-1.194, P 0.011) and Hashimoto's thyroiditis (OR = 1.142, 95% CI 1.026-1.271, P 0.015) on OP. However, no direct causal association was found between hyperthyroidism (OR = 1.030, 95% CI 0.944-1.123, P 0.508) or thyroid cancer (OR = 0.971, 95% CI 0.898-1.051, P 0.469) and OP.

Conclusion: Our MR analysis revealed a causal association between hypothyroidism, Hashimoto's thyroiditis, and OP. This highlights the significant impact of thyroid function on bone health. However, further longitudinal studies are needed to confirm these findings conclusively.

Parathyroid hormone (PTH) is thought to induce remodeling-based bone formation by promoting osteoclastic activity, a process known as cellular coupling. Our research has shown that the frequency of PTH administration affects trabecular number and thickness. High-frequency PTH administration induced remodeling-based bone formation, while less frequent administration induced both remodeling-based and modeling-based bone formation. Additionally, we found that specific bone sites influence whether remodeling-based or modeling-based bone formation is more likely to occur. Additionally, while PTH significantly increases trabecular bone, it also causes cortical porosis. Our research on the femoral diaphysis showed that PTH administration resulted in the invasion of blood vessels and osteoclasts into the cortical bone. Abaloparatide acts similarly to teriparatide through the parathyroid hormone receptor type 1 (PTH1R) but may have a wider anabolic window due to its lesser impact on bone resorption. Our mouse studies with abaloparatide showed similar results to those seen in human patients, with increased preosteoblastic cell populations and wider anabolic windows when compared with teriparatide. Abaloparatide-induced bone formation cannot be explained solely by remodeling-based bone formation, indicating the need for further research into modeling-based bone formation.

Background: The fibula, situated laterally in the leg, receives vital nutrition through nutrient arteries during embryonic bone growth and early ossification. This study aims to assess the direction, distance, location, number, and foraminal index of nutrient foramina in dry fibulae from the South Indian population.

Materials and methods: A descriptive cross-sectional analysis involved 63 dry adult human fibulae sourced from the Department of Anatomy, Saveetha Medical College and Hospital, Thandalam. Parameters like fibula length, location, number, and direction of vascular foramina were recorded. Statistical analyses were performed on morphometric data and foraminal index.

Results: The mean fibula length was 34.68 ± 2.11 cm. Among the fibulae, 88.88% had a single nutrient foramen, 4.76% had dual foramina, and 6.34% lacked nutrient foramina. Most single foramina were found on the medial crest (66.66%), followed by between the medial crest and posterior border (20.63%). Nutrient foramina were primarily located in Zone II (87.30%), followed by Zone III (11.11%) and Zone I (1.58%). Directionally, 85.71% pointed downward, while 14.28% pointed upward. The mean foraminal index was 40.85 ± 6.78, ranging from 32.57 to 56.25.

Conclusion: Zone II, particularly on the medial crest, was the most prevalent location for vascular foramina in the fibula. Dual foramina occurred in 6.34% of cases. This precise anatomical knowledge is valuable for various medical professionals, including anthropologists, forensic experts, radiologists, plastic surgeons, and orthopedic surgeons, especially in procedures involving vascularized fibular bone grafts.

Introduction: Achondroplasia (ACH) is a common skeletal dysplasia associated with short-limbed short stature caused by gain-of-function mutations in the fibroblast growth factor receptor 3 (FGFR3) gene. Meclozine was found to inhibit FGFR3 signaling using a drug repositioning strategy. In some countries, growth hormone (GH) has been employed to ameliorate short stature in children with ACH. This study aims to investigate the effects of meclozine and GH on bone growth and quality using an experimental model of ACH.

Materials and methods: Meclozine (2 mg/kg/day) and/or GH (0.35 mg/kg/day) were administered to a mouse model of ACH from the age of 7 to 56 days. Body length and body weight of each mouse were measured during these treatments. At the end of treatments, these mice were subjected to micro-computed tomography scans to measure the lengths of long bones and bone mineral density (BMD). The width of the growth plate was quantified by histological analysis.

Results: The body and bone length of transgenic mice significantly increased after treatment with meclozine and GH, although there was no additive effect of the combination therapy on promoting bone growth. In contrast, BMD was additively increased by the combination therapy. The width of the growth plate in transgenic mice was significantly increased by both treatments, although the hypertrophic zone was enlarged by meclozine but not by GH.

Conclusion: Meclozine or GH may be an option for treating children with ACH to ameliorate bone length and quality, but the additive effect would be limited.

Introduction: To explore the possible associations between blood markers including albumin, hemoglobulin, creatinine and 25 OH vitamin D with sarcopenia using the ISarcoPRM algorithm.

Materials and methods: A total of 2094 community-dwelling males and postmenopausal females (495 males, 1599 females)aged ≥ 50 years were recruited and their demographic data along with all comorbidities and laboratory evaluations were noted. Functional measurements were also quantified and the ISarcoPRM algorithm was used for the diagnosis/confirmation of the participants into sarcopenic and non-sarcopenic categories.

Results: Sarcopenia was detected in 434 (20.7%) participants and low albumin level in 578 (27.6%) of them. While sarcopenia was detected in 193 (33.4%) of 578 subjects with low albumin levels, and in 241 (15.9%) of 1516 subjects with normal albumin levels (p < 0.001). In the binary logistic regression analysis, among the blood parameters; only albumin levels [OR: 0.932 (95% CI 0.876-0.992) in males (p = 0.026), OR: 0.901 (95% CI 0.862-0.941) in females (p < 0.001)were found to be independently associated with sarcopenia in each gender. After adjusting for sociodemographic and other clinical factors, having low albumin levels(≤ 4.0 g/dL) were independently associated with sarcopenia i.e. 2.368 times (95% CI 1.424-3.939) in males and 2.026 times (95% CI 1.520-2.699) in females (both p < 0.001).

Conclusion: Independent of other factors, low albumin level is associated with sarcopenia i.e. at least two times in both genders. Older and obese adults at risk of malnutrition should be screened/diagnosed and treated early for sarcopenia. Prospective studies are needed for better/prompt management of relevant patients who are prone to significant morbidity and mortality.

Introduction: The purpose of this study was to evaluate the impact of disease activity and gonadal status on bone mineral density (BMD) and turnover markers (BTMs) in individuals with acromegaly.

Materials and methods: Subjects underwent laboratory tests for PTH, 25-hydroxyvitamin D, calcium, phosphorus, osteocalcin (OC) and C-telopeptide (CTX-1) and bone densitometry at the lumbar spine (LS), femoral neck (FN) and total hip (TH).

Results: Sixty participants (48.6 ± 11.0 years; 66,7% female) were included in this cross-sectional study. Phosphorus, OC, CTX-1, and LS BMD were greater in the active disease group than in the controlled/cured disease group (P = 0.025, P < 0.001, P = 0.007, and P = 0.016, respectively). When analyzing gonadal status, phosphorus, OC and CTX-1 were greater in the hypogonadal group than in the eugonadal group (P = 0.017, P = 0.015, and P = 0.033, respectively). Patients with hypogonadism had a higher prevalence of reduced bone mass compared to eugonadal patients (44 vs. 17%, P = 0.023).

Conclusion: This study revealed increased levels of phosphorus and BTMs in patients with active acromegaly. In this group, the greater LS BMD values are likely due to the anabolic effects of GH and IGF-1 and/or to the influence of LS arthropathy. Moreover, hypogonadism negatively impacts bone metabolism in acromegaly, leading to elevated BTMs and a higher prevalence of reduced bone mass in individuals affected by both conditions.

Introduction: The risk of postoperative sequelae and in-hospital mortality in Japanese patients aged 90 years and older with hip fractures is unexplored. This study aims to use a comprehensive medical claims database in Japan to compare super-elderly patients aged 90 years and older with elderly aged 65-89 and clarify the risk of sequelae and in-hospital mortality in super-elderly patients.

Materials and methods: We retrospectively analyzed the Diagnosis Procedure Combination (DPC) database for all of Japan from April 2016 to March 2022. Medical records from approximately 1100 DPC-related hospitals were provided with consistent consent during this period. In this study, we focused on super-elderly patients and examined the association with the risk of postoperative pneumonia, pulmonary embolism, myocardial infarction, urinary tract infection, acute renal dysfunction, subsequent cognitive dysfunction, and in-hospital mortality after one-to-one propensity score matching.

Results: After performing propensity score matching based on sex and comorbidities, 129,953 pairs of patients were identified. These pairs were compared to elderly and super-elderly patients. The results of this study showed that compared with hip fractures in the elderly, hip fractures in the super-elderly were associated with an increased risk of pneumonia, urinary tract infection, acute renal dysfunction, subsequent cognitive dysfunction, and in-hospital mortality after adjustment for confounders. The odds ratio of in-hospital mortality was 2.190 (95% CI 2.062-2.325).

Conclusion: As it has been shown that super-elderly patients with hip fractures are at greater risk of respiratory and urinary tract infections and increased in-hospital mortality, careful attention should be required for perioperative management.