JBMR Plus最新文献

Bone has the fascinating ability to self-regenerate. However, under certain conditions, such as type 2 diabetes mellitus (T2DM), this ability is impaired. T2DM is a chronic metabolic disease known by the presence of elevated blood glucose levels that is associated with reduced bone regeneration capability, high fracture risk, and eventual non-union risk after a fracture. Several mechanical and biological factors relevant to bone regeneration have been shown to be affected in a diabetic environment. However, whether impaired bone regeneration in T2DM can be explained due to mechanical or biological alterations remains unknown. To elucidate the relevance of either one, the aim of this study was to investigate the relative contribution of T2DM-related alterations on either cellular activity or mechanical stimuli driving bone regeneration. A previously validated in silico computer modeling approach that was capable of explaining bone regeneration in uneventful conditions of healing was further developed to investigate bone regeneration in T2DM. Aspects analyzed included the presence of mesenchymal stromal cells (MSCs), cellular migration, proliferation, differentiation, apoptosis, and cellular mechanosensitivity. To further verify the computer model findings against in vivo data, an experimental setup was replicated, in which regeneration was compared in healthy and diabetic after a rat femur bone osteotomy stabilized with plate fixation. We found that mechanical alterations had little effect on the reduced bone regeneration in T2DM and that alterations in MSC proliferation, MSC migration, and osteoblast differentiation had the highest effect. In silico predictions of regenerated bone in T2DM matched qualitatively and quantitatively those from ex vivo μCT at 12 weeks post-surgery when reduced cellular activities reported in previous in vitro and in vivo studies were included in the model. The presented findings here could have clinical implications in the treatment of bone fractures in patients with T2DM. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

This study aimed to investigate the association between daily sleep duration of <7 hours and lower bone mineral density (BMD) using data from annual health check-ups conducted in Japan between 2020 and 2022. Multivariate regression models were used, where BMD was the objective variable and daily sleep duration (<5 hours, 5 to <7 hours, 7 to <9 hours [reference], ≥9 hours) was the exposure variable adjusted for age, body mass index, physical activity, smoking status, and alcohol intake for men and women and further adjusted for menopausal status for women. The association between insomnia and BMD was also investigated. BMD was determined using calcaneal quantitative ultrasound and expressed as a percentage of the young adult mean (%YAM). In total, 896 men and 821 women were included. Median age was 54 years (interquartile range [IQR]: 46 to 64) for men and 55 years (IQR: 46 to 64) for women). Median BMD for men and women was 79%YAM (IQR: 71 to 89) and 75%YAM (IQR: 68 to 84), respectively. Approximately 80% of men and women slept <7 hours daily. Multivariate regression showed no association between sleep duration and BMD in men. However, women who slept 5 to <7 hours daily had significantly higher BMD by 3.9% compared with those who slept 7 to<9 hours (p = 0.004). No association between insomnia and BMD was found. Overall, a daily sleep duration of <7 hours was not independently associated with lower BMD compared to those who slept 7 to <9 hours in men and women. However, as there is evidence of both shorter and longer sleep durations being associated with an increased risk of adverse events, including cardiovascular events, our result needs to be interpreted with caution. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

The association between prevalent fractures and tooth loss in postmenopausal women remains unclear. Herein, we investigated the association between prevalent vertebral and nonvertebral fractures, the number of teeth present at baseline, and the number of teeth lost during follow-up in postmenopausal Japanese women. This cross-sectional study enrolled 843 participants (mean age 68.3 years). The number of teeth at follow-up was evaluated in 655 women in this longitudinal study. The participants were divided into four groups according to their prevalent fracture status: no fractures, vertebral fractures alone, nonvertebral fractures alone, and both fracture types. After adjusting for covariates, Poisson regression analyses were performed to investigate differences in the number of teeth at baseline and that lost during the follow-up period among the four groups. Participants with prevalent vertebral fractures alone had significantly fewer teeth at baseline than those in participants without fractures or nonvertebral fractures alone (p < 0.001 for both). Furthermore, they lost more teeth during the follow-up period than did those with no fractures (p = 0.021) and tended to lose more teeth than did those with nonvertebral fractures alone or both prevalent fracture types. We observed no significant difference in the number of teeth lost between the participants with nonvertebral fractures alone and those with no fractures. Postmenopausal women with prevalent vertebral fractures may be at a higher risk of tooth loss. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Rapid and extensive sublesional bone loss after spinal cord injury (SCI) is a difficult medical problem that has been refractory to available interventions except the antiresorptive agent denosumab (DMAB). While DMAB has shown some efficacy in inhibiting bone loss, its concurrent inhibition of bone formation limits its use. Sialic acid-binding immunoglobulin-like lectin (Siglec)-15 is expressed on the cell surface of mature osteoclasts. Anti-Siglec-15 antibody (Ab) has been shown to inhibit osteoclast maturation and bone resorption while maintaining osteoblast activity, which is distinct from current antiresorptive agents that inhibit the activity of both osteoclasts and osteoblasts. The goal of the present study is to test a Siglec-15 Ab (NP159) as a new treatment option to prevent bone loss in an acute SCI model. To this end, 4-month-old male Wistar rats underwent complete spinal cord transection and were treated with either vehicle or NP159 at 20 mg/kg once every 2 weeks for 8 weeks. SCI results in significant decreases in bone mineral density (BMD, −18.7%), trabecular bone volume (−43.1%), trabecular connectivity (−59.7%), and bone stiffness (−76.3%) at the distal femur. Treatment with NP159 almost completely prevents the aforementioned deterioration of bone after SCI. Blood and histomorphometric analyses revealed that NP159 is able to greatly inhibit bone resorption while maintaining bone formation after acute SCI. In ex vivo cultures of bone marrow cells, NP159 reduces osteoclastogenesis while increasing osteoblastogenesis. In summary, treatment with NP159 almost fully prevents sublesional loss of BMD and metaphysis trabecular bone volume and preserves bone strength in a rat model of acute SCI. Because of its unique ability to reduce osteoclastogenesis and bone resorption while promoting osteoblastogenesis to maintain bone formation, Siglec-15 Ab may hold greater promise as a therapeutic agent, compared with the exclusively antiresorptive or anabolic agents that are currently used, in mitigating the striking bone loss that occurs after SCI or other conditions associated with severe immobilization. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

Monogenic diabetes, including mitochondrial diabetes, constitutes 1% to 3% of all diabetes. Although there is an increased interest in understanding the mechanisms of bone fragility in people with diabetes, skeletal research is mostly focused on type 1 and type 2 diabetes. Little is known on skeletal health among people with mitochondrial diabetes. In this single-center study, we presented clinical characteristics of individuals with mitochondrial diabetes and clinical diagnosis of osteoporosis. Of 10 patients with mitochondrial diabetes, 4 (40%) had a clinical diagnosis of osteoporosis. Patients with osteoporosis were older, had lower body mass index, longer diabetes duration, lower fasting C-peptide, and presence of multiple comorbidities compared with patients without osteoporosis. In addition to our cases, we also systematically reviewed literature on skeletal health in people with mitochondrial diabetes and provided an overview of potential factors affecting skeletal health and future clinical and research directions to improve the care of people with mitochondrial disease. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Diabetes poses a significant risk to bone health, with Type 1 diabetes (T1D) having a more detrimental impact than Type 2 diabetes (T2D). The group of hormones known as incretins, which includes gastric inhibitory peptide (GIP) and glucagon-like peptide 1 (GLP-1), play a role in regulating bowel function and insulin secretion during feeding. GLP-1 receptor agonists (GLP-1 RAs) are emerging as the primary treatment choice in T2D, particularly when atherosclerotic cardiovascular disease is present. Dipeptidyl peptidase 4 inhibitors (DPP-4is), although less potent than GLP-1 RAs, can also be used. Additionally, GLP-1 RAs, either alone or in combination with GIP, may be employed to address overweight and obesity. Since feeding influences bone turnover, a relationship has been established between incretins and bone health. To explore this relationship, we conducted a systematic literature review following the PRISMA guidelines. While some studies on cells and animals have suggested positive effects of incretins on bone cells, turnover, and bone density, human studies have yielded either no or limited and conflicting results regarding their impact on bone mineral density (BMD) and fracture risk. The effect on fracture risk may vary depending on the choice of comparison drug and the duration of follow-up, which was often limited in several studies. Nevertheless, GLP-1 RAs may hold promise for people with T2D who have multiple fracture risk factors and poor metabolic control. Furthermore, a potential new area of interest is the use of GLP-1 RAs in fracture prevention among overweight and obese people. Based on this systematic review, existing evidence remains insufficient to support a positive or a superior effect on bone health to reduce fracture risk in people with T2D. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

A 39-year-old female with a history of kidney transplant presented to the endocrinology clinic for osteoporosis evaluation after sustaining an ankle fracture from a fall. Her kidney transplant regimen (mycophenolate mofetil 360 mg twice a day, tacrolimus 0.5 mg every morning and 0.5–1 mg every evening, prednisone 5 mg/day) and baseline creatinine (1.0–1.2 mg/dL) had been stable for several years. After an appropriate secondary workup, she was started on abaloparatide 80 μg subcutaneous daily injections for osteoporosis. She had a good initial biochemical response to therapy. However, 5 months after abaloparatide initiation she was found to have a new elevation in serum creatinine (1.17 to 1.69 mg/dL) despite stable serum tacrolimus trough levels, and two new human leukocyte antigen (HLA) antibodies (anti-HLA antibodies detected to Cw7 and DP28). Abaloparatide was stopped due to concern for immunogenicity. There was no evidence of rejection on kidney biopsy and she was restabilized on her transplant regimen with a new baseline creatinine of 1.3–1.6 mg/dL. The patient was subsequently started on teriparatide 20 μg daily subcutaneous injections for 2 years with good biochemical response, significant improvement in bone mineral density, and stable transplant regimen without additional signs of immunogenicity or rejection. This is the first case report to raise concern about immunogenicity with abaloparatide in solid organ transplant recipients. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Type 1 diabetes (T1D) confers an increased risk of fracture and is associated with lower bone mineral density (BMD) and altered microarchitecture compared with controls. Adequate calcium (Ca) intake promotes bone mineralization, thereby increasing BMD. The objective of this analysis was to evaluate the associations of total daily Ca intake with bone outcomes among youth with T1D. This was a cross-sectional analysis of girls ages 10–16 years with (n = 62) and without (n = 60) T1D. We measured Ca intake with a validated food-frequency questionnaire and BMD, microarchitecture, and strength estimates with dual-energy X-ray absorptiometry and high-resolution peripheral quantitative computed tomography. Total daily Ca intake did not differ between groups (950 ± 488 in T1D versus 862 ± 461 mg/d in controls, p = 0.306). Serum 25OHD was lower in T1D (26.3 ± 7.6 versus 32.6 ± 9.0 ng/mL, p = <0.001), and parathyroid hormone (PTH) was higher in T1D (38.9 ± 11 versus 33.4 ± 9.7 pg/mL, p = 0.004). Trabecular volumetric BMD and thickness at the tibia were lower in T1D (p = 0.013, p = 0.030). Ca intake correlated with trabecular BMD at the radius and tibia among T1D participants (β = 0.27, p = 0.047, and β = 0.28, p = 0.027, β = 0.28, respectively) but not among controls (p_interaction = 0.009 at the radius, p_interaction = 0.010 at the tibia). Similarly, Ca intake was associated with estimated failure load at the tibia in T1D but not control participants (p = 0.038, β = 0.18; p_interaction = 0.051). We observed the expected negative association of Ca intake with parathyroid hormone in controls (p = 0.022, β = −0.29) but not in T1D participants (p_interaction = 0.022). Average glycemia as measured by hemoglobin A1c did not influence the relationship of Ca and PTH among participants with T1D (p_interaction = 0.138). These data suggest that youth with T1D may be particularly vulnerable to dietary Ca insufficiency. Increasing Ca intake may be an effective strategy to optimize bone health in this population. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

Chronic nonbacterial osteomyelitis (CNO) is a rare disease spectrum affecting children and adults. Adult CNO may occur as isolated bone inflammation, or with a broad range of extraskeletal features. CNO pathophysiology, including the key drivers of inflammation, remains largely unknown. For pediatric CNO, a role for pro-inflammatory cytokine dysregulation has been proposed, but studies in adults are scarce. We therefore provide immunological characterization of adult CNO. Cross-sectional study in our referral center including adult CNO patients (n = 172) and healthy controls (n = 65). Inflammation parameters and systemic inflammatory based scores(SIBS, including neutrophil/lymphocyte ratio [NLR] and systemic immune inflammation index [SII]) were compared between groups. Cytokine expression was explored with electrochemiluminescent immunoassays in 33 patients, eight healthy controls and 21 osteoporosis patients. Routine inflammation markers were higher in patients than in controls, but generally remained within reference range. Systemic inflammation was more pronounced in patients with additional vertebral involvement as compared to those osteitis in the anterior chest wall alone, in patients with comorbid pustulosis palmoplantaris or psoriasis, and in patients with strongly rather than moderately increased lesional uptake on nuclear imaging. SII was elevated in CNO patients too, but NLR was not. Cytokine expression was generally nondifferential between patients and both control groups, and patients displayed low absolute concentrations of pro-inflammatory cytokines. In this adult CNO cohort, systemic inflammation was generally subtle, but more pronounced in patients with vertebral lesions, associated skin disease, and strongly increased uptake on nuclear imaging. SII was increased in patients compared to healthy controls. Contrasting pediatric studies, we found no increased expression of the pro-inflammatory cytokines that have been proposed to drive the inflammatory cascade, like interleukin-6, -8, and -17 (IL-6, IL-8, and IL-17), and tumor necrosis α (TNF-α). Further studies are needed to evaluate the use of SII in diagnosis and monitoring of CNO, and elucidate the role of cytokine dysregulation in adult disease. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.