Journal of Bone and Mineral Research最新文献

Atypical femur fractures (AFFs) have been reported with long-term use of anti-resorptive drugs. Early identification is crucial because it allows early intervention to stop the progression to complete fracture, thus potentially reducing the ensuing burden. It has been shown that extending the scan image to take a full-length image of the femur (FFI) using single energy (SE) X-rays at the time of a dual-energy X-ray absorptiometry (DXA) scan can detect findings in the spectrum of AFF. Following the International Society for Clinical Densitometry (ISCD) recommendations, FFI by SE X-ray is being performed for all patients who present to the Calcium Metabolism and Osteoporosis program at AUBMC for bone mineral density measurement by DXA, if they have received anti-resorptive drug for a cumulative period of 3 years or more. Patients can be currently on anti-resorptive drug or have discontinued it within the past 5 years prior to scan, instead of the 1 year, as recommended by the ISCD. The primary aim of this retrospective study was to assess the prevalence of findings in the spectrum of AFF using FFI by SE X-rays. We collected data on demographic factors, clinical risk factors for osteoporosis, and bone densitometry parameters. Out of the 948 patients, 18 patients were found to have findings in the spectrum of AFF; 14 underwent subsequent imaging studies to investigate and confirm these abnormalities. One patient out of 948 patients was found to have an incomplete AFF confirmed by computed tomography scan. Studying the prevalence of the signs of AFF on FFI in other studies and assessing the specificity of this technique by comparing its findings with more established methods is important. Future ISCD task forces may need to reassess efficacy and cost effectiveness of its recommended guidance on using SE femur in patients to prevent adverse outcomes.

X-linked osteoporosis, caused by PLS3 genetic variants, is a rare bone disease, clinically affecting mainly men. Limited data are available on bone microarchitecture and genotype-phenotype correlations in this disease. Our aims were to assess bone microarchitecture and strength in adults with PLS3 variants using high-resolution peripheral quantitative computed tomography (HR-pQCT) and to explore differences in the phenotype from HR-pQCT between PLS3 variants. HR-pQCT scans were obtained from the distal radius and tibia of 13 men and 3 women with PLS3 variants. Results were compared with age- and sex-matched controls from a normative dataset from literature and expressed as Z-scores. Median age was 46 yr for men and 48 yr for women. In men, total bone area was large (median Z-score: 1.33 radius; 1.46 tibia) due to a large trabecular area (+1.73 radius; +1.87 tibia), while the cortical area was small (-2.61 radius; -2.84 tibia). Total volumetric bone mineral density (BMD) was low due to low trabecular (-3.46 radius; -3.37 tibia) and cortical BMD (-2.87 radius; -2.26 tibia). Regarding bone microarchitecture, the largest deviations were found in trabecular number (-2.18 radius; -1.64 tibia), trabecular separation (+2.32 radius; +1.65 tibia), and cortical thickness (-2.99 radius; -2.46 tibia), whereas trabecular thickness and cortical porosity were normal (-0.36 and -0.58 radius; 0.09 and -0.79 tibia). Additionally, failure load was low (-2.39 radius; -2.2 tibia). Results in the women deviated less from normative data. Men with frameshift/nonsense variants seemed to have more deviant trabecular and cortical microarchitecture and strength, at both scan locations, than those with missense/in-frame insertion variants. In conclusion, HR-pQCT provides valuable insights into bone area, BMD, microarchitecture, and strength in adults with PLS3 variants and can be used to explore genotype-phenotype relationships. Longitudinal analyses in larger groups are needed to study the natural course of the disease and treatment effects.

A 58-yr-old woman presented to our mineral metabolism center, complaining of localized and continuous pain, which worsened with movements, and weakness of the right foot. The patient reported having had a fracture of the fifth metatarsal bone of the right foot about 4 mo ago. She was initially treated with a cast that she did not tolerate and then with an orthopedic brace. After about 1 mo, she noticed swelling of the right foot and started complaining of continuous pain. The physical examination when came to our center seemed partly improved in respect to the initial one referred by the patient even though she still presented with a mild swelling, reddish skin color, and mild sweating on the right foot. Allodynia and hyperalgesia still persisted but at a lower grade. Main biochemical parameters of calcium metabolism were in the normal range. After excluding other clinical conditions, a diagnosis of complex regional pain syndrome type I was made. She was treated with neridronate iv with resolution of symptoms while continuing with physical therapy and pain relievers. Similar milder episodes were reported by the patient in the following months. However, they were immediately resolved by prompt neridronate infusion. No further complaints have been reported during the next 3 yr follow-up.

Osteogenesis imperfecta (OI) is a multisystem disorder most often caused by pathogenic variants in genes that encode type I collagen. Type I collagen is abundant not only in bone but also in multiple tissues including skin, tendons, cornea, blood vessels, and heart. Thus, OI can be expected to affect cardiovascular system, and there are numerous reports of cardiovascular disease (CVD) in people with OI. However, there is no consensus on how CVD in OI should be assessed or managed. To fill this gap, a multidisciplinary group was convened to develop clinical guidance. The work included a systematic review of the available literature and, using a modified Delphi approach, the development of a series of statements summarizing current knowledge. Fourteen clinical recommendations were developed to guide clinicians, patients, and stakeholders about an approach for CVD in adults with OI. This paper describes how the work was conducted and provides the background and rationale for each recommendation. Furthermore, we highlight knowledge gaps and suggest research priorities for the future study of CVD in OI.

Background: Chronic stress leads to elevated stress hormones, which may be linked to bone breakdown. Puerto Rican adults living on the US mainland have higher prevalence of stress than the general population, and higher and/or similar prevalence of osteoporosis compared with non-Hispanic Whites. The role of stress on bone remains unclear and may be modified by diet. A Dietary Approaches to Stop Hypertension (DASH) pattern, as a measure of dietary quality, was most protective for bone outcomes among Puerto Ricans.

Methods: In this cross-sectional study, 958 Boston Puerto Rican Health Study participants were included (aged: 59.9 ± 7.6 y). Stress markers (epinephrine, norepinephrine, cortisol) were collected via 12-hr urine samples and elevated concentrations were categorized using sex-specific cut-offs. Bone mineral density (BMD) was assessed via dual energy x-ray absorptiometry. Analysis of covariance models with least squares means were used to test differences in mean BMD between participants with elevated and non-elevated stress markers. Multivariable logistic regression examined associations between stress markers and osteoporosis in post-menopausal females and males. Models were adjusted for age, height, smoking, alcohol use, education, glucocorticoid use, and diabetes.

Results: Higher urinary epinephrine was associated with lower BMD at the lumbar spine (P=.012), femoral neck (P=.005), trochanter (P<.001), and total hip (P<.001) in Puerto Rican adults, and with higher odds of osteoporosis among males (OR = 4.01 [95%CI: 1.11, 14.5], P=.03). An interaction between DASH and norepinephrine was noted for post-menopausal females at the lumbar spine. No associations were noted for norepinephrine or cortisol (P>.11), although higher urinary norepinephrine was associated with lower lumbar spine BMD in post-menopausal females not taking estrogen, with lower adherence to DASH (P=.03).

Conclusion: Higher urinary epinephrine and norepinephrine were associated with poorer bone outcomes in Puerto Rican adults, in a sex-specific manner, warranting future longitudinal studies to clarify associations. Dietary quality may moderate these associations.

Romosozumab following anti-resorptive can be an effective sequential treatment strategy to improve bone strength. However, whether the transition to romosozumab after denosumab is associated with greater improvement in bone mineral density (BMD) and trabecular bone score (TBS) compared with denosumab continuation remains unclear. In this propensity score-matched cohort study, we analyzed data from postmenopausal women who initiated denosumab between 2017 and 2020. Individuals who were transited to 12 mo of romosozumab after denosumab were 1:1 matched to those who continued an additional 12 mo of denosumab (n = 86 for each group; denosumab-romosozumab [DR] and denosumab-denosumab [DD]). Mean BMD gain by denosumab treatment in matched DR and DD groups from denosumab initiation to transition (median 4 times [range 2-8]) was +4.8% and +2.0% in the lumbar spine (LS) and total hip, respectively. DR group showed greater LS BMD gain compared with the DD group (+6.8 vs +3.3% point, p<.001) for 12 mo post-transition independent of the duration of prior denosumab treatment, yielding greater overall LS BMD gain in DR compared with DD (+11.6% vs +8.0%, p<.001). DD group showed continued improvement of hip BMD, whereas hip BMD was maintained but not improved in the DR group. DR group was associated with greater TBS improvement than the DD group (2.9% vs 1.0%, p = .042). One month after the transition to romosozumab from denosumab, P1NP immediately increased above the level of denosumab initiation with relatively suppressed CTx, creating a transient anabolic window. For 12 mo follow-up, 1 incident morphometric vertebral fracture and 1 patella fracture were observed in DD, whereas 1 ankle fracture was observed in the DR group. Romosozumab following denosumab improved LS BMD and TBS greater than denosumab continuation in postmenopausal women.

Upon completing romosozumab therapy for osteoporosis, sequential treatment with other agents is required. However, for patients at high fracture risk despite such therapy, re-administration of romosozumab might be a potent subsequent option to prevent additional fractures. Currently, there is insufficient real-world clinical data verifying the efficacy of romosozumab re-administration. This study evaluated its efficacy. We enrolled 72 osteoporosis patients who remained at high risk of fractures after a 12-mo course of romosozumab, followed by sequential therapy either with bisphosphonates, denosumab, or teriparatide. Patients were re-administered another 12-mo romosozumab to assess changes in bone mineral density (BMD) and the percentages of patients achieving a T-score > -2.5 at the completion. Our result exhibited that BMD at the lumbar spine and femoral neck increased significantly through the re-administration phase (p < .001). The percentage of patients achieving a T-score > -2.5 in the lumbar spine, total hip and femoral neck increased significantly compared to before initial romosozumab therapy, with the greatest improvement seen after re-administration (all p < .001). Bone formation markers increased significantly (p < .001) during re-administration, while resorption markers showed no significant change (p = .408). The impact of prior sequential therapy was also evaluated. BMD increased significantly at all sites for patients who received bisphosphonates as sequential therapy (p < .05). After denosumab therapy, significant BMD increases were observed only in the lumbar spine (p < .01), while the total hip and femoral neck showed no significant change. After teriparatide therapy, BMD temporarily decreased during the sequential period but increased significantly after romosozumab re-administration, especially in the lumbar spine and femoral neck (both p < .001). In conclusion, romosozumab re-administration is an effective treatment. Furthermore, its efficacy varies depending on the sequential therapy used, with the highest effectiveness seen in the order of teriparatide, bisphosphonates, and denosumab.

Osteonecrosis of the jaw (ONJ) is a severe disease leading to decreased quality of life, but risk factors for ONJ in chronic kidney disease (CKD) patients remain unclear. We conducted a nested case-control study using a large Japanese administrative database to investigate. CKD patients were identified based on estimated glomerular filtration rate (eGFR) measurements, and ONJ cases were identified using ICD-10 codes and diagnostic terms. Controls were matched 1:4 by age and sex. Among 597 026 CKD patients, 75 ONJ cases were identified during a median follow-up of 2.9 yr (incidence rate: 3.27 per 100 000 patient-years). A total of 375 patients (250 males, 66.7%) with a median age of 72 yr (interquartile range (IQR), 64-78) were included after matching controls. The use of bisphosphonates and denosumab for tumor-related disorders in the case group was significantly higher compared to the control group. There was no significant association between kidney functions and the ONJ risk. Multivariate analysis revealed that anti-resorptive drugs for tumor-related disorders [odds ratio (OR): 74.74, 95% confidence interval (CI): 8.81-634.39, p<.001] and oral corticosteroids (OR: 13.23, 95% CI: 3.34-52.33, p<.001) were significantly associated with increased ONJ risk, while anti-resorptive drugs for osteoporosis and injectable corticosteroid use were not. Other relevant factors such as diabetes, liver disease, anabolic drugs, and radiation therapy did not have a significant association with ONJ risk. When stratified by indications for bisphosphonate use (known to be eliminated by renal excretion), bisphosphonate use for tumor-related disorders showed a significant association with ONJ risk (OR: 27.80, 95% CI: 2.47-313.29, p<.01), while bisphosphonates use for osteoporosis did not (OR: 0.74, 95% CI: 0.19-2.92, p=.67). These findings suggest that anti-resorptive drugs for tumor-related disorders and oral corticosteroids are associated with ONJ risk in CKD patients. Heightened surveillance may be necessary for CKD patients receiving these treatments to prevent or detect ONJ early.