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Objective: Osteoarthritis (OA) is a common and degenerative joint disorder in the elderly. A greater importance of understanding the relationship between genetic factors and OA prevalence has emerged with population aging. We therefore investigated the associations of several bone disease-related genetic variants with the prevalence of OA and osteoporosis in Japanese elderly women from the Obuse study cohort, which was randomly sampled from a basic town resident registry.Methods and Results: In total, 206 female participants (mean ± standard deviation age: 69.7 ± 11.0 years) who completed OA, bone mineral density, and genotype assessments were included. The number of patients diagnosed as having knee/hip OA and osteoporosis was 59 (28.6%) and 30 (14.6%), respectively. Fisher's exact testing revealed significant relationships between the minor T allele of LDL receptor related protein 5 (LRP5) rs3736228 and the prevalence of knee/hip OA and osteoporosis. The respective odds ratios (ORs) of the TT genotype for knee/hip OA and osteoporosis were 7.28 (95% confidence interval [CI] 2.22-28.08) and 5.24 (95% CI 0.95-26.98). An additional subgroup analysis for knee OA revealed that the frequency of the common C allele of methylenetetrahydrofolate reductase (MTHFR) rs1801133 had a statistically significant protective association with the prevalence of knee OA (OR 0.58, 95% CI 0.35-0.97).Conclusion: In sum, the present study demonstrated significant associations of LRP5 rs3736228 and MTHFR rs1801133 with knee/hip OA and osteoporosis prevalences and knee OA prevalence, respectively, in Japanese elderly women. These results will help further the understanding of OA pathogenesis and related genetic risk factors. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to evaluate the short- to mid-term clinical results of posterior-stabilized trabecular metal total knee arthroplasty (TKA) with cementless fixation of all components and investigate the radiographic changes of tibial and patellar components and cut bone surfaces over time.Methods: We retrospectively collected the data of 128 knees from 88 consecutive patients who had undergone initial TKA with NexGen LPS-Flex TM implants. A total of 66 knees from 45 patients (mean ± standard deviation age: 70.3 ± 7.5 years) met the selection criteria, which had been employed cementless fixation of all parts and at least 3 years of postoperative follow-up duration. Clinical evaluations included range of motion, conventional knee score, function score, postoperative complications, and revision. For radiological evaluations, the bone contact surface of each implant was divided into 7 zones for tibial component and 2 zones for patellar component. Each region was examined immediately after surgery, at 6 and 12 months, and then every year afterwards.Results: The mean observation period of 45 subjects was 4.2 years. Adequate fixation of tibial components was maintained during follow-up, although the patellar components of 2 knees required revision after repeated falls. No loosening was observed in any implants. The initial gap in tibial components disappeared in all knees, and a reactive line remained in 4 knees. There were no revisions, except for 2 cases, which were ascribed to patellar component fracture caused by repeated falls.Conclusion: Cementless posterior-stabilized trabecular metal TKA appears to be a good surgical option. Longer-term examination for revision cases is required to validate our results. [ABSTRACT FROM AUTHOR]

Appropriate management for osteoporosis in adult patients with Prader-Willi syndrome (PWS) has not been established. We report on a 21-year-old woman with PWS, who underwent denosumab treatment for osteoporosis. She presented with fractures and was shown to have very low bone mineral density (BMD), while she had been treated with supplementation of growth hormone for 7-14 years of age and estrogen from 15 years of age. BMD was monitored in the total hip region by dual-energy X-ray absorptiometry. Laboratory tests included bone-specific alkaline phosphatase, urinary type I collagen amino-terminal telopeptide, tartrate-resistant acid phosphatase 5b, 1-alpha, 25-dihydroxyvitamin D3, and parathyroid hormone. BMD and laboratory data were evaluated before and at 4, 8, and 13 months of treatment. After 13 months of denosumab therapy, BMD increased by 4.5%, and bone turnover markers notably improved. No fractures occurred. To the best of our knowledge, this is the first report to describe the clinical outcomes of denosumab treatment for osteoporosis in patients with PWS. Based on our findings, denosumab could represent an effective treatment option for osteoporosis in PWS patients. [ABSTRACT FROM AUTHOR]

Background: The natural history and pathogenesis of the skeletal abnormalities found in neurofibromatosis type 1 (NF1) are poorly understood, and the therapeutic options for these manifestations remain limited. This report first describes the clinical outcomes of denosumab treatment for a patient with NF1 suffering from osteoporosis. Methods: We enrolled a patient with NF1 under denosumab treatment for osteoporosis, prior fractures, and no improvement in bone mineral density (BMD) over 3 years of alendronate therapy. BMD was monitored by dual-energy X-ray absorptiometry. Tested laboratory data included bone-specific alkaline phosphatase, urinary type I collagen amino-terminal telopeptide, tartrate-resistant acid phosphatase 5b, 1-alpha, 25-dihydroxyvitamin D3, and parathyroid hormone. BMD and laboratory data were evaluated before, between 2 and 4 months, and at 6, 12, 18, and 24 months of treatment. Case presentation: During 2 years of denosumab therapy for osteoporosis in a 58-year-old female NF1 patient with prior fractures, BMD increased by 6.5% in the lumbar spine and 10.6% in the total hips, and bone turnover markers were notably improved. No fractures occurred during the latter half of treatment. Conclusion: Denosumab represents an effective treatment option for osteoporosis in NF1 patients. [ABSTRACT FROM AUTHOR]

Background: Multiple-system atrophy (MSA) is an α-synucleinopathy with a very aggressive course and poor prognosis, which lacks efficient treatment. Thus, MSA represents a serious health and social problem. Progressive stridor and acute laryngeal obstruction likely occur in MSA; however, little is known about the bone metabolism or efficacy of bone absorption drugs, such as denosumab, in osteoporosis with MSA.Case Presentation and Methods: Two male patients with osteoporosis in MSA presented to our institution (at 54 and 68 years of age). Denosumab was started after the diagnosis of osteoporosis in MSA, and the therapy was continued for 18-24 months.Results: Lumbar and hip bone mineral density showed a 3.5% and 0.6% increase at 24 months or a 10.3% and 3.2% increase at 18 months, respectively. Bone turnover markers were also improved in the two cases during follow-up. No fractures or other complications were recorded during the observation period.Conclusion: This is the first study describing osteoporosis in two patients with MSA being treated by osteoporotic treatment. Based on our findings, it can be concluded that denosumab may be an effective therapy for osteoporosis in MSA. [ABSTRACT FROM AUTHOR]

Low bone mineral density (BMD) is one of the most frequent complications of anorexia nervosa (AN). We report the clinical outcomes of a female patient with severe AN, whose chest had become deformed due to thoracic fracture. Lumbar BMD was 0.358 g/cm2 (T-score = -6.3), and total hip BMD was 0.411 g/cm2 (T-score = -4.4). Active vitamin D increased these parameters by 81.0% and 57.4%, respectively, but a drop in her nutrition status afterward resulted in a sharp decrease in BMD values. These findings suggest that adequate nutrient intake is essential for effective osteoporosis treatment in patients with AN. [ABSTRACT FROM AUTHOR]

Background: While it is well known that teriparatide (TPTD) increases bone mineral density (BMD) in osteoporotic patients, it is unknown whether TPTD pretreatment affects BMD after denosumab (DMAb) therapy.Methods: Fifty-seven patients in TPTD-pretreated group and 35 patients in DMAb-alone group had been further analyzed, all of whom were treated by DMAb for 1.5 years. Vitamin D (400 IU) and Ca (600 mg) supplementation was used in all patients. The BMD of lumbar 1-4 vertebrae (L-BMD), bilateral total hips (H-BMD), and bilateral femoral neck (FN-BMD) was quantified at first visit, and at 4, 8, 12, and 18 months after daily TPTD treatment following four times DMAb treatment.Results: There were significant differences in L-BMD (p=0.004) and H-BMD (p=0.026) at baseline between TPTD-pretreated and DMAb-alone groups, although there was no significant difference in FN-BMD between the two groups. The increase of L-BMD by DMAb therapy was less in TPTD-pretreated group than in DMAb-alone group. There was no significant difference in H-BMD, although percent changes of H-BMD tended to be higher in the TPTD-pretreated group than those in the DMAb-alone group. Percent change in FN-BMD at 4 months (p=0.067) and 12 months (p=0.057) tended to be higher in TPTD-pretreated group than in DMAb-alone group. Percent change in FN-BMD at 18 months was significantly higher in TPTD-pretreated group (p=0.004) than in DMAb-alone group.Conclusion: These findings suggest that the pretreatment of TPTD might have enhanced the increase of BMD in cortical bones treated by DMAb. Thus, it is favorable that TPTD can be used for osteoporotic patients who have high fracture risks with cortical bones. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to evaluate the effects of denosumab in patients with osteoporosis (OP) and non-metastatic breast cancer following treatment of 1) surgery, 2) surgery and aromatase inhibitors, and 3) surgery, aromatase inhibitors, and anti-cancer agents, compared with those in primary OP patients. Patients and methods: In this retrospective 24-month study, patients were divided into the primary OP group (34 cases) or OP receiving breast cancer treatment group (breast cancer group; 17 cases). We measured serum calcium, whole parathyroid hormone (PTH), 1,25OH2D3, bone alkaline phosphatase (BAP), tartrate-resistant acid phosphatase-5b (TRACP-5b), and bone mineral density (BMD) of the lumbar 1-4 vertebrae (L-BMD) and bilateral total hips (H-BMD) for 24 months. Results: The percent changes of serum calcium in the breast cancer group were significantly lower than those in the primary OP group at 1 week, 1 and 12 months. The percent changes of whole PTH in the primary OP group were significantly lower than those in the breast cancer group at 2 and 4 months. Significant differences were found between the groups at 18 months (-34.5% in the primary OP group and -52.6% in the breast cancer group, respectively) for the percent changes of BAP. Significant differences were found between the groups at 12, 18, and 24 months (-39.7% in the primary OP group and -64.0% in the breast cancer group at 24 months, respectively) for the percent changes of TRACP-5b. The percent changes of L-BMD and H-BMD were significantly increased at 12, 18, and 24 months in both the primary OP group (7.0% and 4.7% at 24 months, respectively) and breast cancer group (8.0% and 5.4% at 24 months, respectively), compared with pre-treatment levels. Significant differences were not found between the groups for the percent changes of L-BMD and H-BMD. Conclusion: Denosumab significantly increased L-BMD and H-BMD to comparable degrees in both groups; therefore, it represents a good therapeutic option for OP receiving breast cancer treatment as well as primary OP. Also, vitamin D supplementation is required due to the potential hypocalcemia, and estrogen may be responsible for the decrease of serum calcium in the breast cancer patients. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this 18-month retrospective study was to evaluate the differences in outcomes of denosumab with tumor necrosis factor (TNF) inhibitors (TNFis), tocilizumab (TCZ), or abatacept (ABT) treatment in osteoporosis (OP) patients with rheumatoid arthritis (RA). Patients and methods: Patients were divided into TNFis-treated (TNF group; 44 cases), TCZ-treated (TCZ group; 8 cases), or ABT-treated (ABT group; 14 cases) groups. We measured serum bone-specific alkaline phosphatase (BAP) and tartrate-resistant acid phosphatase 5b (TRACP-5b) at baseline and every 3 months for 18 months and assessed bone mineral density (BMD) of the lumbar 1-4 vertebrae (L-BMD) and total hip BMD (H-BMD) at baseline and every 6 months for 18 months. Results: There were no significant differences in the percent changes in BAP, TRACP-5b, or L-BMD among the groups. The percent change in H-BMD was significantly increased in the TCZ group at 12 months or at 12 and 18 months, compared with that in the ABT group or TNF group, respectively. The percent change in L-BMD was significantly increased at 12 months in the TCZ and TNF groups, and at 18 months in all the 3 groups compared with pretreatment levels, whereas the percent change in H-BMD was significantly higher at 6, 12, and 18 months in the TCZ group, at 12 and 18 months in the TNF group, and at 18 months in the ABT group, compared with pretreatment levels. Conclusion: Our findings suggest that TCZ might be more useful than TNF or ABT in light of the observed H-BMD increases with denosumab therapy for OP patients with RA. [ABSTRACT FROM AUTHOR]

A worldwide health concern, osteoporosis (OP), increases the risk of bone fracture and results in morbidity. This study examined whether the representative bone absorption marker serum tartrate-resistant acid phosphatase 5b (TRACP-5b) or bone formation marker bone alkaline phosphatase (BAP) could estimate primary OP status and denosumab efficacy in a real-world setting. We retrospectively enrolled 114 female postmenopausal primary OP patients in Japan. Values and percent changes in TRACP-5b, BAP, lumbar 1-4 bone mineral density (L-BMD), and total hip BMD (H-BMD) were assessed before treatment and at 4, 8, and 12 months of therapy to identify the correlations between the percent changes in bone metabolic markers and BMD. We also established two sets of subgroups based on the upper limits of reference values in Japan for serum: TRACP-5b (<420 mU/dL) and (≥420 mU/dL) and BAP (<14.5 µg/L) and (≥14.5 µg/L). Negative correlations were observed for the percent changes of TRACP-5b and H-BMD at 4 months (r=-0.3476) and 8 months (r=-0.3880), for the percent changes of BAP and H-BMD at 8 months (r=-0.3354), and for the percent changes of BAP and L-BMD at 12 months (r=-0.3186). We observed a significant difference between the subgroups for the percent changes of L-BMD at 8 months (p=0.013) and 12 months (p=0.004) in BAP values. These results suggest that TRACP-5b and BAP had negative correlations with BMD, and that BAP represented a useful serum marker to evaluate L-BMD during denosumab therapy for OP. [ABSTRACT FROM AUTHOR]

The syndrome of pregnancy- and lactation-associated osteoporosis is a rare disorder whose precise etiology and treatment are largely unknown. We herein report two such cases occurring in the early postpartum period that led to multiple fragility compression fractures. Combination therapy of vitamin D and vitamin K enabled a marked gradual increase in bone mineral density. [ABSTRACT FROM AUTHOR]