Journal of Bone Metabolism最新文献

This review aims to synthesize current knowledge regarding the use of bisphosphonates (BPs) in the treatment of bone complications in patients with neurofibromatosis type 1 (NF1). NF1 is a genetic disorder marked by multiple benign tumors of the nervous system and various skeletal abnormalities, such as osteoporosis and an increased risk of fractures. BPs are drugs that inhibit bone resorption, commonly used to treat osteoporosis and other bone diseases. The review identified multiple studies examining the effects of BP therapy in NF1 patients. Most studies reported improvements in bone mineral density and reduced fracture occurrence. The most commonly reported side effects were mild gastrointestinal symptoms and transient musculoskeletal pain. However, the evidence is limited by the small number of studies and the heterogeneity of patient populations and treatment protocols. In conclusion, BPs show improvements in managing NF1 complications such as osteoporosis and a reduction of fracture risk in NF1 patients. While the existing studies suggest positive outcomes, there is a need for more rigorous, large-scale studies to establish standardized treatment protocols and long-term safety profiles. Healthcare providers should consider BP therapy as a potential option for NF1 patients with significant bone complications, while also monitoring for possible adverse effects.

Background: Osteoporosis is a significant public health issue in aging populations. Despite advances in pharmacotherapy, underdiagnosis and undertreatment remain prevalent even in patients with recent fractures. This study examined 20-year trends (2002- 2022) in anti-osteoporotic medication (AOM) usage in South Korea.

Methods: Data from the Korean National Health Information Database were retrospectively analyzed. The study included individuals aged ≥50 years and analyzed prescription trends, medication adherence, measured by the medication possession ratio (MPR), and treatment initiation rates post-fracture. The AOMs examined included bisphosphonates, selective estrogen receptor modulators, denosumab (DMAB), teriparatide (TPTD), and romosozumab (ROMO).

Results: Over two decades, AOM use has shifted significantly from oral to injectable formulations, with injectables surpassing oral medications in 2020; from 397,440 prescriptions in 2016 to 1,162,779 in 2022. Prescriptions for DMAB surged following its approval as a first-line therapy in 2019, increasing 2.65 times from 217,606 in 2019 to 575,595 in 2022. The MPR improved from 35.4% in 2003 to 73.2% in 2021, with females demonstrating higher adherence than males. Post-fracture treatment rates increased from 31.1% in 2006 to 39.9% in 2021 but remained below 50%. Vertebral fractures had the highest treatment initiation rates, while anabolic agents, such as TPTD and ROMO were underprescribed despite their efficacy.

Conclusions: This 20-year analysis highlights significant progress in osteoporosis management in South Korea, including a shift towards injectable therapies and improved adherence. However, the persistent undertreatment of high-risk patients underscores the requirement for enhanced access to anabolic agents, clinician education, and policy reforms to optimize post-fracture care.

Background: Bone-target agents (BTAs), including denosumab (DMAb), are one of the bone metastasis treatments that should continue indefinitely. However, BTAs may be interrupted in some cases. In osteoporosis, DMAb withdrawal causes a rebound effect characterized by an increased bone turnover with spine fractures and hypercalcemia; evidence of the DMAb withdrawal effect in oncology is lacking.

Methods: This study aimed to identify the DMAb withdrawal effect amongst lung cancer patients treated with DMAb for bone metastases between January 2020 and December 2021. Patients who discontinued DMAb were included. Encounter notes, radiological and laboratory findings were comprehensively reviewed.

Results: Thirty patients were included with a median follow-up of 21 months (interquartile range [IQR], 10-30) after DMAb discontinuation. Bisphosphonates were administered before starting DMAb in 7 patients (23.3%) and after DMAb withdrawal in 4 cases (13.3%). Three cases of DMAb withdrawal-related hypercalcemia and 3 cases of spine fractures following DMAb cessation were identified in 5 patients (16.7%), all of them were females and the median age was 65 years old (IQR, 65-70). No statistical difference in DMAb duration or number of injections was found in patients developing DMAb withdrawal-related spine fractures or hypercalcemia compared with others (binary logistic regression, p=0.688 and p=0.938, respectively).

Conclusions: Patients with bony-metastatic lung cancer, especially post-menopausal women, are at risk of fractures and calcium abnormalities after DMAb discontinuation, suggesting that DMAb withdrawal effect may also be present in the oncological setting. A close follow-up and careful monitoring during and after discontinuation of DMAb is necessary.

Background: Quantitative computed tomography (QCT) is essential for assessing osteoporosis and monitoring spinal deformities. "Clari-QCT," a software that uses artificial intelligence to analyze conventional computed tomography (CT) scans and produce QCTequivalent reports. This study aims to evaluate the effectiveness of Clari-QCT by comparing its results with traditional QCT, with the goal of validating new diagnostic tools for spinal deformities.

Methods: The study analyzed dual energy X-ray absorptiometry, CT, and QCT data from 18 patients at Inha University Hospital. Clari-QCT software was evaluated for its ability to generate QCT-equivalent reports from CT images. The software processes abdomen CT images, calculates bone density in designated slices, and provides bone mineral density (BMD), T-score, and Z-score values. Patients were classified into normal, mild, and severe spinal deformity groups. Intraclass correlation coefficient (ICC) analysis was used to measure the agreement between actual and predicted BMD values.

Results: The study included participants with an average age of 64 and a mean body mass index of 24.88. The average BMD was 94.7 g/cm³ by QCT and 122.5 g/cm³ by Clari- QCT, with individual differences ranging from 4.9 to 61.8. T-score discrepancies ranged from 0.16 to 6.86. ICC analysis showed moderate to high agreement between methods, with ICC1 values of 0.597, ICC2 of 0.64, ICC3 of 0.81, and ICC1k, ICC2k, ICC3k values ranging from 0.748 to 0.895.

Conclusions: Clari-QCT demonstrates good agreement with actual QCT measurements in normal and severe spinal deformity groups but shows reduced accuracy in patients with mild deformities. If the limitations are addressed, it could become a useful tool for monitoring bone health in patients with spinal deformities.

Background: Osteoporosis is a significant global public health issue, increasingly affecting younger individuals and placing substantial economic burdens on society. Risk factors vary, with non-modifiable ones like age and ethnicity, as well as modifiable factors including corticosteroid use, caffeine intake, and reduced exercise. This study examines the relationship between bone density, body components, and physical activity (PA) in enhancing bone health, particularly in obese athletes.

Methods: The 66 participants aged 18 to 30 were classified into two groups: 34 obese and 32 athletes. Measured parameters included body composition through bioelectrical impedance analysis, and bone mineral density (BMD) via quantitative ultrasound, while PA was assessed using the International PA Questionnaire.

Results: Our findings revealed a significant positive correlation between BMD and PA (r=0.284, P=0.023). Additionally, PA demonstrated strong negative correlations with body mass index (BMI), fat mass, and visceral fat (r=-0.738, r=-0.733, and r=-0.704 respectively, all P<0.001). In contrast, no significant correlation was observed between PA and lean mass (r=0.065, P=0.609). BMD was negatively associated with BMI and visceral fat, while a robust correlation between basal metabolic rate and lean mass was evident.

Conclusions: A study comparing athletes involved in high-impact sports indicated that these athletes maintained adequate BMD for their chronological age (Z-score≥-2.0). Moreover, a significant difference in BMD was observed when comparing the athletes to the obese group(P=0.018).

Romosozumab, which is approved for the treatment of osteoporosis, has a dual-action mechanism that promotes bone formation and inhibits bone resorption. However, its association with an increased risk of major adverse cardiovascular events, as highlighted in the ARCH I study, raises concerns. The underlying pathophysiological mechanisms, possibly involving changes in platelet dynamics, are yet to be fully elucidated. Herein, we present a case of a 60-year-old Korean woman diagnosed with immune thrombocytopenic purpura and new-onset osteoporosis, who was treated with romosozumab. Subsequent to the administration of romosozumab, there was a notable elevation in her platelet count. This observation warrants further investigation into the off-target effects of romosozumab, especially its impact on hematopoietic stem cell function and platelet dynamics. This case accentuates the imperative for more comprehensive research into the systemic effects of romosozumab, particularly its involvement in hematopoiesis and cardiovascular risk, to thoroughly understand its extensive implications for patient health.

Background: There are age- and sex-related increases in the prevalence of osteoporosis. Bone densitometry based on dual energy X-ray absorptiometry (DXA) is the gold standard for the assessment of bone mineral density (BMD). Three-dimensional (3D) analysis of the proximal femur (3D-DXA) allows discrimination between cortical and trabecular compartments, and it has shown a good correlation with computed tomography. We aimed to assess age- and sex-related volumetric density differences in trabecular and cortical bone using 3D-DXA and determine the reference intervals for integral volumetric (v)BMD within the Argentine population.

Methods: Healthy female and male adult subjects (N=1,354) from Argentina were included. Hip BMD was measured using DXA, and 3D analysis was performed using 3D-Shaper software. The integral vBMD, cortical surface BMD, and trabecular vBMD (trab vBMD) were measured.

Results: The study population included 73.9% women (N=1,001) and 26.13% men (N=353). We found a significant decrease in integral vBMD between 20 and 90 years in both sexes (women, -23.1%; men, -16.6%). Bone loss indicated in the integral vBMD results was mainly due to a decrease in trabecular bone in both sexes (women, -33.4%; men, -27.7%). The age-related loss of cortical bone density was less and was limited to the female population, without no age-related differences in men. Moreover, 3D-DXA allowed us to propose reference intervals for integral vBMD.

Conclusions: We found age- and sex-related bone loss between 20 and 90 years in an Argentine cohort via integral vBMD measurements using 3D-DXA, mainly due to decreases in trabecular bone in both sexes. The age-related loss of cortical bone density was less and was limited to the female population.

Background: This review explores the discriminative ability of fracture risk assessment tool (FRAX) in major osteoporotic fracture (MOF) and hip fracture (HF) risk prediction and the densitometric diagnosis of osteoporosis in Asian populations.

Methods: We systematically searched the EMBASE, Cochrane, and PubMed databases from the earliest indexing date to January 2024. Studies were included if FRAX was used to identify future osteoporotic fractures or a densitometric diagnosis of osteoporosis in an Asian population and reported the area under the curve (AUC) values. Meta-analyses were conducted after quality assessment for AUC with 95% confidence intervals across the following categories: standard FRAX without/with bone mineral density (BMD), adjusted FRAX, and BMD alone for fracture prediction, as well as standard FRAX for densitometric diagnosis of osteoporosis.

Results: A total of 42 studies were included. The AUC values for predicting fracture risk using FRAX-MOF with BMD (0.73 [0.70-0.77]) was highest compared to FRAX-MOF without BMD (0.72 [0.66-0.77]), and adjusted FRAX-MOF (0.71 [0.65-0.77]). The AUC values for predicting fracture risk using FRAX-HF with BMD (0.77 [0.71-0.83]) was highest compared to FRAX-HF without BMD (0.72 [0.65-0.80]), and adjusted FRAX-HF (0.75 [0.63-0.86]). The AUC values for BMD alone (0.68 [0.62-0.73]) was lowest for fracture prediction. The AUC values for identifying a densitometric diagnosis of osteoporosis was 0.77 [0.70-0.84] and 0.76 [0.67-0.86] using FRAX-MOF and FRAX-HF, respectively.

Conclusions: FRAX with BMD tends to perform more reliably in predicting HF compared to MOF in Asia. However, its accuracy in predicting fracture risk in Asian populations can be improved through region-specific, long-term epidemiological data.

Background: Osteogenesis imperfecta (OI) is a rare disease with an estimated incidence of between 1/25,000 and 1/10,000 globally. The main treatment for OI is the administration of bisphosphonate drugs. Research on clinical, radiographic, and biochemical markers to monitor patients with OI treated with zoledronate can be challenging in countries in which patients have limited national health insurance. We aimed to examine patients with OI treated in Indonesia with a minimum follow-up period of 2 years.

Methods: An observational study was conducted of all patients with OI treated with zoledronate between 2021 and 2023 at a tertiary hospital in Indonesia. We evaluated the paediatric quality of life (PedsQL), bone mineral density (BMD), and alkaline phosphatase (ALP) level before and after zoledronate treatment. To monitor safety, serum creatinine and calcium levels were also measured.

Results: Eleven boys (55%) and nine girls (45%), with an average age of 6.9 years (range, 4-17 years), were included. After 2 years of zoledronate treatment, the total PedsQL score increased from 66.7 to 76.9 (P=0.0001) and the mean lumbar and total body BMD increased from 0.467 and 0.501 to 0.599 g/cm2, and 0.626 g/cm2 (P=0.001), respectively. The ALP level decreased from 310.6 to 186.4 mg/mL (P=0.0001). Neither serum creatinine (P=0.586) nor calcium (P=0.53) levels changed from the pre-treatment to 2 years post-treatment time points.

Conclusions: Zoledronate was safe and effective for the treatment of OI. There were significant improvements in the quality of life and BMD in patients with OI. The ALP level decreased, but serum creatinine and calcium levels were not affected by zoledronate.

Chronic kidney disease (CKD) often leads to mineral and bone disorders (CKD-MBDs), which are nearly universal in patients undergoing dialysis. CKD-MBD includes abnormal calcium-phosphate metabolism, vascular and soft tissue calcification, and bone abnormalities (renal osteodystrophy [ROD]). Bone fragility in CKD occurs due to low bone mass and poor bone quality, and patients with CKD have higher fracture and mortality rates. Bone histomorphometry is the gold standard for ROD diagnosis; however, it is labor-intensive and expensive. The Kidney Disease Improving Global Outcomes clinical practice guidelines on CKD-MBD suggest serum parathyroid hormone (PTH) and bone-specific alkaline phosphatase (bone ALP) for predicting bone turnover in ROD. In this review, we focus on the role of PTH and bone turnover markers, intact procollagen type N-terminal propeptide of type I collagen, bone ALP, and tartrate-resistant acid phosphatase 5b in diagnosing ROD, predicting fractures, and guiding treatment in patients with CKD.