Journal of Bone and Mineral Metabolism最新文献

Introduction: Though low serum magnesium (Mg) levels are associated with adverse outcomes in patients on haemodialysis, the interaction with calcimimetics remains uncertain. We hypothesized a potential interaction between serum Mg levels and calcimimetic use in cardiovascular events (CVEs), all-cause mortality, and new fractures during follow-up in patients on haemodialysis.

Materials and methods: This single-centre retrospective cohort included 399 Japanese adults on maintenance haemodialysis, followed for ≤ 5 years. Cox models with time-dependent serum Mg levels and calcimimetic usage interaction adjusted for clinicodemographic and biochemical covariates.

Results: At baseline, 205 patients (51.4%) were prescribed calcimimetics (median serum Mg, 2.5 mg/dL). The mean observational period was 40.6 months, and 122 CVEs, 159 all-cause mortality, and 69 new fractures occurred (incidence rates: 0.09, 0.10-, and 0.05 per patient-year), respectively. The time-dependent model showed serum Mg < 2.4 mg/dL was associated with a markedly higher risk for new fractures in calcimimetic-naïve patients. Serum Mg levels were not significantly associated with CVEs and all-cause mortality, regardless of calcimimetic usage. The restricted cubic spline curve demonstrated linear inverse trends of serum Mg levels with all-cause mortality and new fractures in calcimimetic-naïve patients. However, no significant interaction between Mg and calcimimetic use was observed for any outcome.

Conclusion: We did not detect a statistically significant interaction between serum Mg levels and calcimimetic use. Nonetheless, low serum Mg (< 2.4 mg/dL) was associated with a higher risk of fractures, particularly among calcimimetic-naïve patients. Thus, low serum Mg is a potentially modifiable risk marker associated with fracture risk, particularly in calcimimetic-naïve patients.

Introduction: Studies launched in Japan on once-weekly teriparatide (1/W-TPTD) and twice-weekly teriparatide (2/W-TPTD) are limited. Therefore, we examined the effects of sequential therapy using anti-resorptive agents after administering 1/W-TPTD and 2/W-TPTD using dual-energy X-ray absorptiometry (DXA) and DXA-based 3D modeling.

Materials and methods: This was a multicenter retrospective study following a phase 3 clinical trial called the TWICE study. Two-year follow-up data were collected after administering 1/W-TPTD or 2/W-TPTD for 1 year (follow-up after the phase 3 clinical trial).

Results: 20 subjects in the group of pre-treatments with 1/W-TPTD followed by sequential administration of bisphosphonate or denosumab (1/W-TPTD [BP/denosumab]), and 22 in the group 2/W-TPTD (BP/denosumab) were included in the analysis of changes in the BMD by post-treatment. In the 1/W-TPTD (BP/denosumab) group, a significant increase in L2-4 BMD was observed. In the 2/W-TPTD (BP/denosumab) group, a significant increase in total hip, neck, and L2-4 BMD values was observed. Analysis by 3D-SHAPER revealed that both the 1/W-TPTD (BP/denosumab) and 2/W-TPTD (BP/denosumab) groups demonstrated significant increases in cortical sBMD and vBMD 2 years after the initiation of post-treatment.

Conclusion: In subjects who received 1/W-TPTD and 2/W-TPTD for about 1 year followed by sequential administration of BP or denosumab, significant improvements in BMD were continuously observed. Furthermore, significant improvements in cortical sBMD and vBMD were also demonstrated by analysis using 3D-SHAPER. Both 1/W-TPTD and 2/W-TPTD were effective in the treatment of osteoporosis by using anti-resorptive agents for sequential administration.

Background: Skeletal stem cells (SSCs) underlie skeletal development, homeostasis, regeneration, and aging, yet their identities and functions are highly heterogeneous across anatomical sites and life stages. Mouse genetic studies have identified multiple SSC populations-each residing in distinct niches such as the growth plate, periosteum, and bone marrow-and revealed their dynamic regulation across developmental, homeostatic, regenerative, and aging contexts. However, translating these insights to humans remains challenging due to species differences and limited access to physiological human skeletal tissues. This review synthesizes current understanding of SSC diversity and how distinct compartments contribute to skeletal formation and maintenance throughout life. It also summarizes emerging human skeletal modeling strategies, including pluripotent stem cell differentiation, bioengineered in vitro systems, and in vivo transplantation, evaluating their ability to reconstruct skeletal components and SSC-bearing niches. Although recent models reproduce partial structures such as perichondrium-like layers or bone marrow-like microenvironments, most remain compartment-specific and lack integrated, stage-aware architectures that recapitulate physiological SSC behavior and skeletal functions in vivo. We propose an SSC-centric framework that incorporates spatiotemporal diversity, multi-compartment integration, physiological cues, and cross-validation with human tissues, providing predictive and translational platforms for skeletal biology, disease modeling, and regenerative medicine.

Introduction: Surgery has increasingly been reported as an effective treatment for medication-related osteonecrosis of the jaw (MRONJ), but concrete intervention criteria are lacking. On computed tomography (CT) images, the boundary between the healthy site and necrotic lesion, which we defined as "MRONJ demarcation line", is sometimes visible. This study aimed to identify the factors associated with this boundary to improve surgical planning.

Materials and methods: 95 patients with MRONJ who underwent their first CT at our institution between May 2010 and June 2022 were included. The Mann-Whitney U test, Fisher's exact test, and multivariate logistic regression analysis were performed. The cumulative incidence rates were calculated using the Kaplan-Meier method. Statistical significance was set at p < 0.05.

Results: MRONJ demarcation line was observed in 63 patients and absent in 32. Significant associations were identified between MRONJ demarcation line formation and denosumab (p = 0.013), antiresorptive agent (ARA) discontinuation (p = 0.024), and periosteal reaction ( p = 0.034). The cumulative incidence rates of MRONJ demarcation line formation at 12, 24, and 36 months after discontinuation of high-dose ARA were 58.0%, 89.2%, and 96.4% for denosumab, and 29.9%, 68.8%, and 88.3% for bisphosphonates, respectively. In the low-dose group, the rates at 12, 24, and 36 months after discontinuation of denosumab were 41.7%, 51.4%, and 63.5%, respectively, while those for bisphosphonates were 22.2%, 35.8%, and 51.1%.

Conclusion: Denosumab administration, ARA discontinuation, and periosteal reaction are significantly associated with the MRONJ demarcation line, which may help in establishing criteria for surgical intervention.