Kousei Yoh

Health-related quality of life (HRQOL) in Japanese osteoporotic patients and its improvement by elcatonin treatment.

Health-related quality of life (HRQOL; “QOL” hereafter) was evaluated in Japanese osteoporotic patients using three questionnaires; the SF-36 (MOS 36-Item Short-Form Health Survey; generic, profile-type), the EQ-5D (Euro Qol-5 Dimensions; generic, preference-based), and the JOQOL (Japanese Osteoporosis Quality of Life 1999; disease-targeted). The eight subscales and two summary scores of the SF-36 were impaired in these patients even after correction for age and sex. The scores on the EQ-5D and JOQOL correlated well with the subscales of the SF-36 that represent the physical aspects of physical function and bodily pain, which suggests that physical aspects are important determinants of overall QOL status in osteoporotic patients. Although the QOL scores did not correlate with bone mineral density, they were markedly influenced by the presence of vertebral fractures. In particular, the presence of two or more vertebral fractures greatly decreased the QOL scores. We then evaluated the QOL scores before and after treatment. The patients were either given calcium supplementation alone or calcium plus once-weekly elcatonin (Elcitonin, Asahi Kasei Pharma, Tokyo, Japan) injection. Elcatonin treatment markedly improved diverse aspects of the QOL, whereas calcium alone did not. The current data suggest that osteoporosis, especially in the presence of vertebral fracture, is associated with compromised QOL, and therapeutic intervention for osteoporosis should be evaluated in terms of QOL, as well as in terms of increases in bone mineral density and fracture prevention.

Guidelines for diagnosis and management of Paget's disease of bone in Japan

We here propose guidelines for the diagnosis and management of Pagets disease of bone (PDB) in Japan. These guidelines provide basic information on the epidemiology, pathophysiology, clinical signs and symptoms, diagnosis, indications for treatment, and available therapy, including orthopedic surgery. PDB is a chronic disorder characterized by focal abnormalities of bone turnover. The characteristic feature of PDB is excessive osteoclastic bone resorption coupled to increased and disorganized bone formation. The most common symptom of PDB is pain in involved bones. The most serious complication of PDB is malignant bone or soft-tissue tumor. PDB is uncommon in Japan; our survey in 2003 found 169 patients with PDB. The prevalence of PDB in Japan is 0.15/100 000; in patients aged 55 years or more, the proportion reaches 0.41/100 000. A careful medical history and physical examination are essential for the diagnosis. The diagnosis of PDB is based on finding the typical features on radiographs. Bone scintigraphy and measurement of serum alkaline phosphatase are sensitive means of screening for PDB. Since PDB is a rare disease in Japan, bone biopsy is quite often used to exclude bone metastases. The only evidence-based indication for treatment of PDB is pain in involved bones. In Japan, etidronate and calcitonin are approved by the Ministry of Health, Labour and Welfare for treating PDB, but currently risedronate is also under development for treating PDB in Japan. Indications for surgical intervention in PDB include unstable fractures, osteoarthritis, malignant soft-tissue tumor, osteosarcoma, and bone deformity.

Prevalence and clinical features of Paget's disease of bone in Japan

The present study aimed to evaluate the prevalence and clinical presentation of Pagets disease of bone (PDB) in Japan. As PDB is a very rare disease in Japan, a nationwide mail survey was conducted targeting doctors in the specialty most frequently diagnosing and treating PDB patients in Japan. First, the literature for all case reports in Japan published between January 1990 and December 2002 was reviewed to determine who was diagnosing and treating PDB in Japan. This literature review for all case reports in Japan revealed that 72.1% of cases in Japan were reported from departments of orthopedic surgery. A nationwide two-phase mail survey was conducted for the departments of orthopedic surgery of 2320 general hospitals accredited by the Japanese Orthopaedic Association. Phase 1 involved determining how many patients with PDB were followed at each hospital. If the answer was one or more, phase 2 of the survey gathered information on the clinical presentation of current patients. The mail survey yielded a final response rate of 75.4% for phase 1 and 87.6% for phase 2. Phase 1 indicated that the prevalence of PDB in Japan is about 2.8 cases per million capita. Phase 2 revealed a slight female predominance, lower frequency of familial clustering, higher frequency of femoral fracture in the affected femur, and a higher ratio of symptomatic PDB in Japan compared with findings in countries displaying a higher prevalence of PDB. The present epidemiological study revealed that the disorder is extremely rare in Japanese individuals, and that some differences exist with regard to the clinical features of PDB between Japanese patients and patients from high-prevalence countries.

Effects of bazedoxifene on bone mineral density, bone turnover, and safety in postmenopausal japanese women with osteoporosis

This randomized, double‐blind, placebo‐controlled, dose‐response late phase 2 study evaluated the efficacy and safety of bazedoxifene in postmenopausal Japanese women 85 years of age or younger with osteoporosis. Eligible subjects received daily treatment with oral doses of bazedoxifene 20 or 40 mg or placebo for 2 years. Efficacy assessments included bone mineral density (BMD) at the lumbar spine and other skeletal sites, bone turnover marker levels, lipid parameters, and incidence of new fractures. Of 429 randomized subjects, 387 were evaluable for efficacy, and 423 were included in the safety analyses (mean age, 64 years). At 2 years, the mean percent changes from baseline in lumbar spine BMD were significantly greater with bazedoxifene 20 and 40 mg (2.43% and 2.74%, respectively) than with placebo (−0.65%, p < .001 for both). Both bazedoxifene doses significantly improved BMD at the total hip, femoral neck, and greater trochanter compared with placebo (p < .001 for all). Decreases in bone turnover markers were observed with bazedoxifene 20 and 40 mg as early as 12 weeks (p < .05 for all) and were sustained throughout the study. Total and low‐density lipoprotein cholesterol levels were significantly decreased from baseline with both bazedoxifene doses compared with placebo (p < .05 for all). Incidences of new vertebral and nonvertebral fractures were similar among the bazedoxifene and placebo groups. Overall, the incidence of adverse events with bazedoxifene 20 and 40 mg was similar to that with placebo. Bazedoxifene significantly improved BMD, reduced bone turnover, and was well tolerated in postmenopausal Japanese women with osteoporosis.

Hereditary hypophosphatemic rickets with hypercalciuria: a study for the phosphate transporter gene type IIc and osteoblastic function

Two cases of hereditary hypophosphatemic rickets with hypercalciuria (HHRH) were reported in Japanese female siblings. Both of them manifested short stature and bowed legs, and biochemical examination revealed hypophosphatemia, phosphaturia, and hypercalciuria. The serum concentrations of 1,25-dihydroxyvitamin D (1,25(OH)2D) were elevated. In the oral phosphate loading test, serum phosphate levels were markedly increased in the HHRH patients, and the elevation was much higher than that in patients affected with X-linked hypophosphatemic rickets (XLH), suggesting the increased gastrointestinal absorption of phosphate in HHRH. Bone histology studies showed increased osteoid surface and width in HHRH, which was compatible with osteomalacia. In the HHRH patients, there were no hypomineralized periosteocytic lesions, which was a hallmark of XLH in bone histology. In one of the HHRH patients, phosphate administration alone almost completely cured the osteomalacia within a year, although pharmacological doses of 1,25(OH)2D3 had little effect. In osteoblasts isolated from a HHRH patient, basal alkaline phosphatase (ALP) activities and osteocalcin syntheses by a physiological concentration of 1,25(OH)2D3 were not stimulated by the increased medium phosphate concentrations from 0.5 to 4 mM. In contrast, these two parameters were stimulated by the increased medium phosphate concentrations both in normal and XLH osteoblasts, although the regulatory patterns of increased osteocalcin syntheses were different from normal to XLH osteoblasts; 2 and 4 mM of phosphate concentrations at least were necessary for normal and XLH osteoblasts, respectively. The gene analysis of phosphate transporter revealed a novel heterozygous mutation (R564C) in the exon of phosphate transporter NPT type IIc. These lines of evidence suggested that the pathogenesis of osteomalacia in HHRH was different from XLH in terms of the utility of phosphate in osteoblasts. These abnormalities were speculated to be associated with the abnormal functions of phosphate transporter gene type IIc, although the exact roles of this phosphate transporter in the human osteoblast are still unknown.

Results of total hip arthroplasty for dialysis arthropathy in long-term hemodialysis patients

BackgroundThe number of hemodialysis patients has progressively increased in Japan. Among the orthopedic complications in this population, chronic hip arthropathy associated with long-term hemodialysis is one of the most devastating problems. Total hip arthroplasty (THA) is often indicated. However, varying results have been reported for THA in these patients. This study was undertaken to assess the risk-benefit ratio of THA performed in patients with dialysis hip arthropathy.MethodsWe evaluated 17 patients (19 hips) with dialysis hip arthropathy who underwent THA. The duration of hemodialysis before surgery ranged from 10 to 27 years. Histological examination of the tissue samples revealed accumulation of amyloid deposits in all cases. Three patients died within 2 years after operation; the remaining 14 patients (16 hips) were followed for a minimum of 3 years.ResultsThe cumulative survival rate of the prostheses in these 16 hips up to the latest follow-up was 94%. Regarding surgery-related complications, deep infection occurred in one hip, and revision THA was required in one patient with recurrent dislocation and aseptic loosening.ConclusionsTHA for dialysis hip arthropathy in long-term hemodialysis patients is associated with substantial local and general risks. Despite the substantial risk, THA for this patient population seems to afford reasonably satisfactory results.

Quality of life in raloxifene-treated Japanese women with postmenopausal osteoporosis: a prospective, postmarketing observational study.

Abstract Objective: To assess changes in quality of life (QOL) and pain in raloxifene-treated Japanese women with postmenopausal osteoporosis. Research design and methods: This prospective, postmarketing observational study was conducted at 60 Japanese hospitals from September 2007 to February 2009 and included Japanese women with postmenopausal osteoporosis who were new to standard treatment with raloxifene (60 mg/day). Primary outcome measures (QOL and pain) were assessed using the Short Form-8 (SF-8), European Quality of Life Instrument (EQ-5D), osteoporosis-specific Japanese Osteoporosis Quality of Life Questionnaire (JOQOL), a visual analogue scale (VAS-pain), and a pain frequency survey. Assessments were performed at baseline and 8 (except JOQOL) and 24 weeks after first administration of raloxifene. Adverse drug reactions were recorded. Japan Pharmaceutical Information Center registration number: JapicCTI-070465. Results: A total of 506 participants, mean (±standard deviation [SD]) age = 70.7 ± 8.7 years, completed ≥1 follow-up assessment and were included in the analyses. All QOL scores increased from baseline during follow-up. All SF-8 domain scores increased significantly from baseline after 8 and 24 weeks (P < 0.001). Mean (±SD) EQ-5D scores increased significantly from baseline (0.70 ± 0.17) by 0.05 ± 0.15 after 8 weeks and 0.07 ± 0.17 after 24 weeks (P < 0.001). The mean (±SD) total JOQOL score increased significantly from baseline (66.8 ± 16.5) by 3.8 ± 11.3 after 24 weeks (P < 0.001). The percentage of participants with a ≥20 mm reduction in VAS-pain was 32.6% (120/368) and 39.5% (115/291) after 8 and 24 weeks, respectively. The frequency of pain reported by participants decreased after 8 and 24 weeks. Forty adverse drug reactions were reported by 34 participants. Limitations: Limitations include the lack of a control group, the possibility of the changes being due to the natural disease course, and potential selection bias. Conclusions: Our findings suggest that standard treatment with raloxifene improves QOL and relieves pain in Japanese women with postmenopausal osteoporosis in a real-world clinical setting.

Clinical usefulness of serum tartrate-resistant fluoride-sensitive acid phosphatase activity in evaluating bone turnover.

Abstract: This study was carried out to evaluate the clinical validity and usefulness of serum tartrate-resistant fluoride-sensitive acid phosphatase (TrFsACP) activity using 2,6-dichloro-4-acetylphenyl phosphate as substrate at pH 6.2 in metabolic bone diseases. The mean Z-scores of TrFsACP activity in patients on hemodialysis were higher than in healthy subjects (male: 2.04 ± 1.98, n = 49, P < .05; female: 1.49 ± 2.43, n = 39, P < .05) and increased with duration of hemodialysis (r = .516, P < .01). Bone alkaline phosphatase also was found to be significantly higher in hemodialysis patients (male: 0.93 ± 1.49, P < .05; female: 1.66 ± 2.42, P < .05) compared with normal subjects; but had lower correlation with duration of hemodialysis than TrFsACP (r = .277, P < .05). Ulcerative colitis (1.37 ± 2.21, n = 15) in males showed a significantly higher Z-score of TrFsACP compared with control subjects (P < .05). The relationship of TrFsACP activity and ultrasound findings (stiffness; speed of sound [SOS]; broadband ultra sound attenuation [BUA]) in healthy women aged 30–75 years (n = 95) were inversely and significantly correlated with stiffness (r = −.465, P < .01), SOS (r = −.484, P < .01), and BUA (r = −.366, P < .01), but were age dependent. TrFsACP activity significantly correlated with stiffness (r = −.521, P < .05) and SOS (r = −.527, P < .05) only in the age group of 46–55 years. BUA (r = −.313, P > .05) did not correlate significantly in any subject in the present study. We conclude that serum TrFsACP activity is useful in the diagnosis and monitoring of bone turnover.

A case of ochronotic arthropathy treated with total hip arthroplasty

Abstract We report a case of ochronotic arthropathy treated with total hip arthroplasty. The articular cartilage of the patients femoral head and synovium displayed black pigmentation. Microscopically, the articular cartilage revealed reddish-brown pigmentation (particularly in deep cartilage), necrotic chondrocytes, and slight black pigmentation in the cytoplasm of chondrocytes. Electron microscopy revealed electron-dense material deposited predominantly along and between collagen fibers.

Pyridinoline cross‐linked carboxy‐terminal telopeptide of type I collagen in uremic hyperparathyroidism

SUMMARY: We compared the serum level of the pyridinoline cross‐linked carboxy‐terminal telopeptide of type I collagen (I‐CTP) with clinical parameters of bone formation and skeletal symptoms to investigate whether I‐CTP can predict the degree of renal osteodystrophy. Serum I‐CTP was measured in 41 patients with secondary hyperparathyroidism who underwent total parathyroidectomy and autoimplantation (PTx). Measurement was done by using radioimmunoassay. Blood samples were collected before surgery and at 1, 3, 6, 9, 12, 15, and 18 months afterwards for the measurement of bone formation parameters. Serum I‐CTP levels were significantly higher in patients with Jensen grade 3–5 renal osteodystrophy than in patients with grade 0–2 renal osteodystrophy. the I‐CTP levels were also significantly higher in patients with bone or joint pain compared with patients without pain. There was a significant negative correlation between the serum I‐CTP level and the lumbar vertebral (L2‐4) bone mineral density. Serum I‐CTP was significantly correlated with the serum levels of alkaline phosphatase, calcium, and phosphate, as well as the serum calcium x phosphate product, and the intact parathyroid hormone level. These findings suggest that serum I‐CTP could be used as a marker for evaluating osteodystrophy in uremic hyperparathyroidism.