Springer Science and Business Media LLC

Apolipoprotein E (Apo E) polymorphism has been implicated in many chronic diseases, including Alzheimer disease and osteoporosis. Significant association of the Apo E4 allele to low bone mineral density (BMD) has been repeatedly reported. We here examined the Apo E genotype frequencies in the Chinese population (n = 692) and its relationship to BMD. A significantly lower frequency (a prevalence of 7%) of the E4 alleles was found in our Chinese subjects compared to that reported in Caucasians (14.7%) or in Japanese (11.7%). However, no significant association between the Apo E4 allele and BMD Z score was observed in our test subjects; this may be due to the rarity of the Apo E4 allele frequency in Chinese, which requires a larger sample size for detection of significant association. Significant associations detected between Apo E2 allele and BMD at the femoral neck in elderly women (P = 0.02) and at the spine in elderly men (P = 0.03) were in the opposite direction and thus regarded as false-positive results. It is concluded that the Apo E4 allele is rare in Chinese, and a larger population size is needed to see if Apo E4 is associated with BMD in Chinese.

The demineralized sections of dentins of rats were mineralized in vitro. The sections were observed with contact microradiography (CMR) and their mineral contents were determined with micro-photometry of CMR films. In the mineralizing solution containing no carbonate, mineral appeared to adhere only on the surface of the demineralized dentins, regardless of their structure or their chemical nature. However, once the demineralized dentins were immersed in a mineralizing solution containing carbonate, the mineralization proceeded continuounly even in mineralizing solution containing no carbonate, suggesting that the action of carbonate participates in the initiation of mineral deposition. The effect of Mg in the mineralizing solution containing carbonate was studied. Mg showed an inhibitory effect in the mineralization of matrices. This effect seemed to participate in the process of growth or increase of precipitation after the initiation.

A few studies have reported the safety of the treatment of elderly osteoporotic patients with chronic kidney disease (CKD) and the possibility of hypocalcemia. The aim of the present study was to examine the relationship between the incidence of hypocalcemia and the CKD stage in elderly osteoporotic patients treated with denosumab. This study was designed as a parallel-group comparison study between the denosumab-associated hypocalcemia (DAH) groups: the concentration of serum calcium was under 8.6 mg/dl and the normal calcium (NC) groups: the concentration of serum calcium was over 8.6 mg/dl. Fifty-two subjects over 70 years old were enrolled in this study, with 16 patients classified into the DAH group and 36 patients assigned to the NC group. All patients were further classified into two subgroups according to their age, into an around 75 years group to clarify the relevance of old age and an around 85 years group and also into a mild CKD group and a moderate CKD group by based on estimated glomerular filtration (eGFR). Serum calcium concentration, tartrate-resistant acid phosphatase (TRACP-5b), and type 1 procollagen N terminal propeptide (P1NP) were measured, and adverse drug reactions were evaluated. The eGFR and serum calcium were significantly lower in the DAH group than in the NC group in the starting phase. Moreover, TRACP-5b was significantly higher in the DAH group than in the NC group in the starting phase. There were no significant differences in P1NP. The incidence of hypocalcemia was significantly higher in the around 85 groups than in the around 75 groups. The frequency of hypocalcemia was also significantly higher in the severe CKD group than in the mild CKD group. Advanced age combined with low eGFR and low serum Ca status appear to be associated with the incidence of hypocalcemia when using denosumab for the treatment of osteoporosis.

Sex-determining region Y (Sry)-box (Sox)9 is required for chondrogenesis as a transcriptional activator of genes related to chondrocyte proliferation, differentiation, and cartilage-specific extracellular matrix. Although there have been studies investigating the Sox9-dependent transcriptional complexes, not all their components have been identified. In the present study, we demonstrated that thyroid hormone receptor-associated protein (THRAP)3 is a component of a SOX9 transcriptional complex by liquid chromatography mass spectrometric analysis of FLAG-tagged Sox9-binding proteins purified from FLAG-HA-tagged Sox9 knock-in mice. Thrap3 knockdown in ATDC5 chondrogenic cells increased the expression of Collagen type II alpha 1 chain (Col2a1) without affecting Sox9 expression. THRAP3 and SOX9 overexpression reduced Col2a1 levels to a greater degree than overexpression of SOX9 alone. The negative regulation of SOX9 transcriptional activity by THRAP3 was mediated by interaction between the proline-, glutamine-, and serine-rich domain of SOX9 and the innominate domain of THRAP3. These results indicate that THRAP3 negatively regulates SOX9 transcriptional activity as a cofactor of a SOX9 transcriptional complex during chondrogenesis.

RANKL, the essential cue for osteoclast differentiation, is the membrane-bound factor expressed by osteoclastogenesis-supporting cells such as osteoblasts and osteocytes. In vivo evidence indicates that RANKL functions as the indispensable and irreplaceable in the program of osteoclast differentiation. The reason why RANKL plays a critical role in osteoclastogenesis is discussed from the viewpoint of the distinct signaling pathways mediated by co-stimulatory receptors and the key transcription factor NFATc1.

Eldecalcitol (ELD), a new active vitamin D3 analog developed in Japan, has attracted attention as an effective osteoporotic therapeutic drug. However, because ELD leads to greater calcium absorption than does conventional active vitamin D3, it has yet to be used in patients with renal insufficiency. Therefore, we evaluated the efficacy and safety of ELD treatment in 27 postmenopausal women receiving maintenance dialysis in our institution and underwent ELD treatment (starting at 0.5 μg/day) for 6 months. The mean serum albumin-corrected calcium (Caalb) level was significantly increased following treatment (9.01 ± 0.60 before versus 9.56 ± 0.55 after treatment, mean ± SD). Severe hypercalcemia was prevented through cessation or adjustment of the dosage of calcium-containing phosphate binders or existing active vitamin D. The mean serum phosphorus and intact parathyroid hormone levels were well-controlled throughout. The median levels of bone turnover markers, bone-specific alkaline phosphatase and tartrate-resistant acid phosphatase-5b were significantly decreased. The mean lumbar spine bone mineral density (BMD) was increased, a significant difference being observed in age-matched Z-scores (−0.60 ± 1.6 versus −0.36 ± 1.5, p = 0.018). The average change in lumbar spine BMD after ELD treatment was 3.10 %, and in patients with a T-score of <−4.0, it was 5.63 %. There was no effect on forearm BMD. Although this study is based on short-term observation in a single institution, our results suggest that ELD could be used to increase bone density in dialysis patients.

This post hoc analysis of the placebo-controlled phase 3 FRAME study assessed the efficacy and safety of romosozumab in a subpopulation of Japanese postmenopausal women with osteoporosis and chronic kidney disease (CKD). Data were analyzed by baseline estimated glomerular filtration rate (eGFR), where < 90 mL/min/1.73 m2 denoted CKD and ≥ 90 mL/min/1.73 m2 indicated normal renal function. Efficacy outcomes included percent change in lumbar spine, total hip, and femoral neck bone mineral density (BMD) at 12 months from baseline (primary) and incidence of new vertebral and non-vertebral fractures. Tolerability was also assessed. Of 489 Japanese patients with available eGFR data, 339 had mild-to-moderate CKD (romosozumab, n = 170; placebo, n = 169) and 150 had normal renal function (romosozumab, n = 75; placebo, n = 75). Compared with placebo, romosozumab increased lumbar spine BMD by 14.8% (95% confidence interval [CI] 13.7–15.9) and 15.2% (95% CI 13.4–16.9) in the eGFR < 90 and ≥ 90 mL/min/1.73 m2 subgroups, total hip BMD by 4.6% (95% CI 3.8–5.4) and 5.5% (95% CI 4.4–6.7), and femoral neck BMD by 4.0% (95% CI 2.9–5.2) and 5.5% (95% CI 3.8–7.1) at 12 months, respectively (all p < 0.001 vs. placebo). New vertebral fracture incidence was numerically lower with romosozumab than placebo at 12 months in both eGFR subgroups, while the incidence of adverse events was similar between subgroups. Romosozumab for 12 months is an effective and well-tolerated treatment option for Japanese patients with osteoporosis and mild-to-moderate CKD.

The purpose of this study was to clarify bone turnover marker levels in rapidly destructive coxopathy (RDC). Twenty patients with RDC (mean age, 72 ± 11 years; 3 men, 17 postmenopausal women), 111 with osteoarthritis (OA) (age, 60 ± 10 years; 15 men, 13 premenopausal women, 83 postmenopausal women), and 18 with osteonecrosis of femoral head (ON) (55 ± 14 years; 11 men, 3 premenopausal women, 4 postmenopausal women), and 100 patients with femoral neck fracture (FNF) (81 ± 10 years; 27 men, 73 postmenopausal women) were included. Serum tartrate-resistant acid phosphatase 5b (TRACP-5b), bone alkaline phosphatase (BAP), matrix metalloproteinase-3 (MMP-3) levels, and bone mineral density (BMD) of proximal femur and lumbar spine were investigated. TRACP-5b levels were significantly higher in RDC than in OA and ON, whereas BAP levels were higher in RDC than in OA (P < 0.05). MMP-3 levels were higher in RDC and ON than in OA (P < 0.05). TRACP-5b were higher in RDC than OA (P < 0.05) and FNF (P < 0.05) in performing propensity score matching; there were no differences in BMD between RDC and OA. TRACP-5b showed the largest area under the curve (AUC, 0.82) according to receiver operating characteristic (ROC) curve analysis for diagnosing RDC against OA and ON. AUCs of BAP and MMP-3 were 0.78 and 0.74. The respective sensitivities and specificities were 70.0 % and 85.3 % for TRACP-5b (cutoff, 623 mU/dl), 95.0 % and 57.1 % for BAP (13.8 U/l), and 70.0 % and 76.4 % for MMP-3 (52.7 ng/ml). The lack of differences in BMD suggested that high bone turnover marker levels may reflect osteoclast cell activation in RDC hips. Serum TRACP-5b and BAP could be RDC markers.