Hiroshi Hagino

Diagnostic criteria for primary osteoporosis: year 2012 revision

In 1995, the Japanese Society for Bone and Mineral Metabolism (now the Japanese Society for Bone and Mineral Research) established the Osteoporosis Diagnostic Criteria Review Committee. Following discussion held at the 13th scientific meeting of the Society in 1996, the Committee, with the consensus of its members, proposed diagnostic criteria for primary osteoporosis. The Committee revised those criteria in 1998 and again in 2000. The Japanese Society for Bone and Mineral Research and Japan Osteoporosis Society Joint Review Committee for the Revision of the Diagnostic Criteria for Primary Osteoporosis aimed at obtaining international consistency and made a revised edition based on the new findings in 2012.

Bisphosphonate-related osteonecrosis of the jaw: position paper from the Allied Task Force Committee of Japanese Society for Bone and Mineral Research, Japan Osteoporosis Society, Japanese Society of Periodontology, Japanese Society for Oral and Maxillofacial Radiology, and Japanese Society of Oral and Maxillofacial Surgeons.

Bisphosphonates (BPs) have been widely, efficiently, and safely used for the treatment of osteoporosis, malignant hypercalcemia, bone metastasis of solid cancers, and multiple myeloma bone diseases. Accumulating recent reports describe that surgical dental treatments in patients with cancer or osteoporosis who have been receiving intravenous or oral BPs are associated with osteonecrosis of the jaw (bisphosphonate-related osteonecrosis of the jaw, BRONJ). The accurate incidence, clinical backgrounds, and pathogenesis of BRONJ have been unclear and appropriate approaches for prevention and treatment have not been established to date. To address the current situation of BRONJ in Japan, the “Allied Task Force Committee of Bisphosphonate-Related Osteonecrosis of the Jaw,” consisting of physicians specializing in bone biology, orthopedic surgery, rheumatology, obstetrics/gynecology, and medical oncology and dentists specializing in oral surgery, periodontology, dental radiology, and oral pathology, was organized. The committee attempted to propose a standard position paper for the treatment of BRONJ. The committee expects that this proposal will provide objective and correct scientific information on BRONJ and will serve as a reference for conducting dental procedures for patients receiving BPs and in designing prevention and treatment of BRONJ. However, because this position paper is not based on direct clinical evidence, it should be used as a reference, and a decision on treatment in each case should be made after an extensive discussion among physicians, dentists/oral surgeons, and the patients.

Dienogest is as effective as intranasal buserelin acetate for the relief of pain symptoms associated with endometriosis—a randomized, double-blind, multicenter, controlled trial

OBJECTIVE To compare the efficacy and safety of dienogest (DNG) with intranasal buserelin acetate (BA) in patients with endometriosis. DESIGN Phase III, randomized, double-blind, multicenter, controlled trial. SETTING Twenty-four study centers in Japan. PATIENT(S) Two hundred seventy-one patients with endometriosis. INTERVENTION(S) Dienogest (2 mg/day, orally) or BA (900 microg/day, intranasally) for 24 weeks. MAIN OUTCOME MEASURE(S) The pre- to posttreatment changes in the scores of five subjective symptoms during nonmenstruation (lower abdominal pain, lumbago, defecation pain, dyspareunia, and pain on internal examination) and two objective findings (induration in the pouch of Douglas and limited uterine mobility). RESULT(S) Dienogest reduced the scores of all symptoms and findings at the end of treatment, and the mean changes in the scores of all symptoms and findings except induration in the pouch of Douglas were comparable to those obtained with BA. Compared with BA, DNG was associated with irregular genital bleeding more frequently and with fewer hot flushes. The reduction in bone mineral density (BMD) during DNG treatment was significantly lower than that during BA treatment. CONCLUSION(S) DNG is as effective as intranasal BA in alleviating endometriosis, and causes less BMD loss.

Randomized Teriparatide [Human Parathyroid Hormone (PTH) 1–34] Once-Weekly Efficacy Research (TOWER) Trial for Examining the Reduction in New Vertebral Fractures in Subjects with Primary Osteoporosis and High Fracture Risk

CONTEXT Weekly teriparatide injection at a dose of 56.5 μg has been shown to increase bone mineral density. OBJECTIVE A phase 3 study was conducted to determine the efficacy of once-weekly teriparatide injection for reducing the incidence of vertebral fractures in patients with osteoporosis. DESIGN AND SETTING In this randomized, multicenter, double-blind, placebo-controlled trial conducted in Japan, the incidence of morphological vertebral fractures by radiographs was assessed. PATIENTS Subjects were 578 Japanese patients between the ages of 65 and 95 yr who had prevalent vertebral fracture. INTERVENTION Subjects were randomly assigned to receive once-weekly s.c. injections of teriparatide (56.5 μg) or placebo for 72 wk. MAIN OUTCOME MEASURE The primary endpoint was the incidence of new vertebral fracture. RESULTS Once-weekly injections of teriparatide reduced the risk of new vertebral fracture with a cumulative incidence of 3.1% in the teriparatide group, compared with 14.5% in the placebo group (P < 0.01), and a relative risk of 0.20 (95% confidence interval, 0.09 to 0.45). At 72 wk, teriparatide administration increased bone mineral density by 6.4, 3.0, and 2.3% at the lumbar spine, the total hip, and the femoral neck, respectively, compared with the placebo (P < 0.01). Adverse events (AE) and the dropout rates by AE were more frequently experienced in the teriparatide group, but AE were generally mild and tolerable. CONCLUSION Weekly s.c. administration of teriparatide at a dose of 56.5 μg may provide another option of anabolic treatments in patients with osteoporosis at higher fracture risk.

Long-term use of dienogest for the treatment of endometriosis

Aim:  To investigate the safety and efficacy of 52 weeks of dienogest treatment in patients with endometriosis.

Guidelines for the use of bone metabolic markers in the diagnosis and treatment of osteoporosis (2012 edition)

Recently the clinical application of bone metabolic markers has achieved significant progress and the measurements of these indices give us a better understanding of the pathogenesis of osteoporosis. Bone metabolic markers were adapted to select drug treatment for osteoporosis and to evaluate drug efficacy. Therefore, the proper application and assessment of bone metabolic markers in clinical practice is very important. To achieve these aims, the committee on the guidelines for the use of biochemical markers of bone turnover in osteoporosis authorized by the Japan Osteoporosis Society has summarized recent progress in bone markers and proposed the proper utilization of bone markers. Although the use of bone metabolic markers now has an important role in the daily management of osteoporosis, their use in Japan is still insufficient because of insurance coverage limitations. Since the Japan Osteoporosis Society first created the 2001 guidelines, new bone metabolic markers have been introduced into clinical practice. The availability of new osteoporosis treatments that promote bone formation has changed the clinical application of bone metabolic markers in current practice. Therefore, revisions to the current clinical practice are needed which led to the proposal to create these new 2012 guidelines.

Effect of parathyroid hormone on cortical bone response to in vivo external loading of the rat tibia.

Abstract Cortical bone responses following administration of parathyroid hormone (PTH) were evaluated using a four-point bending device to clarify the relationship between the effect of PTH and mechanical loading. Female Wistar rats, 36-months-old, were used. Rats were randomized into three groups (n = 10/group), namely PTH-5 (5 μg PTH/kg body weight), PTH-30 (30 μg PTH/kg body weight), and PTH-v (vehicle). PTH (human PTH (1–34)) was injected subcutaneously three times/week for 3 weeks. Loads on the right tibia were applied in vivo at 29.1 ± 0.3 N for 36 cycles at 2 Hz 3 days/week for 3 weeks using four-point bending. The administration of PTH and tibial mechanical loading were performed on the same day. After calcein double labeling, rats were killed and tibial cross-sections were prepared from the region with maximal bending at the central diaphysis. Histomorphometry was performed over the entire periosteal and endocortical surfaces of the tibiae, dividing the periosteum into lateral and medial surfaces. The in vivo average peak tibial strains (predicted) on the lateral periosteal surface were 1392.4, 1421.8 and 1384.7 μstrain in PTH-v, PTH-5 and PTH-30 groups, respectively, showing no significant difference among the three groups. Significant loading-related increases in the bone formation surface, mineral apposition rate, and bone formation rate were observed at the periosteal and endocortical surfaces. Significant differences between PTH groups were also seen. Interaction between mechanical loading and PTH was significant at both periosteal and endocortical surfaces. It is concluded that PTH has a synergistic effect on the cortical bone response to mechanical loading.

Nationwide one-decade survey of hip fractures in Japan

BackgroundTo elucidate the characteristics of hip fractures and the current status of their treatment in Japan, the Japanese Orthopaedic Association (JOA) conducted a nationwide hip fracture survey from 1998 to the present. The aim of the current report was to present the changes in patient distribution by age and fracture type, cause of fracture, treatment selection, and duration of hospitalization for a study period of one decade.MethodsA tally of all hip fractures that occurred in patients between 2001 and 2008 was conducted in JOA-authorized hospitals and in Japanese Clinical Orthopaedic Association (JCOA) hospitals. Registration forms were sent to these hospitals each year, and registration was performed based on their hospital records.ResultsThe mean response rate was 51.8%, and the total number of patients aged ≥35 with new hip fractures between 2001 and 2008 was 402 760. A drastic increase in the number of patients, especially those aged ≥90 was observed over the course of the decade. More trochanteric fractures occurred than neck fractures during the observational period; however, the neck/trochanter ratio increased over time. Simple falls were the most common cause of fracture. About 94% patients were treated surgically with about a 5-day presurgical hospital stay, and the mean hospitalization period was 40.7 days in 2008.ConclusionsThis one-decade survey demonstrated a drastic increase in the number of patients over the course of the decade in Japan. Appropriate treatment and prevention of hip fractures, including the treatment of osteoporosis and more effective interventions for preventing falls, are important issues to address to reduce the burden of this fracture.

A double-blinded head-to-head trial of minodronate and alendronate in women with postmenopausal osteoporosis

INTRODUCTION In a randomized, active-controlled, double-blinded, multicenter study, the efficacy and safety of minodronate were examined and compared to that of alendronate. METHODS A total of 270 postmenopausal osteoporotic women >or=45 years of age were randomized into the minodronate group (n=135) or alendronate group (n=135). Each subject received 1 mg minodronate or 5 mg alendronate once a day for 12 months. RESULTS Both treatment groups showed similar changes in BMD after 12 months. After 1 year of treatment, the lumbar spine BMD increased by 5.86% and 6.29% in the minodronate and alendronate groups, respectively, and the total hip BMD increased by 3.47% and 3.27%, respectively. Bone turnover markers were rapidly reduced within 1 month in both treatment groups. Urine DPD was significantly lower in the minodronate group than in the alendronate group at 6 months, and urine NTX was significantly lower in the minodronate group than in the alendronate group at 1 and 9 months. Both completion rates for the 12-month study and the overall incidence of clinical adverse events, including gastrointestinal events, were similar between the two groups. CONCLUSIONS The effects on lumbar and hip BMD and the safety profile of minodronate are comparable to those of alendronate. Minodronate is a promising new potent bisphosphonate for the treatment of osteoporosis.

Risk factors for second hip fractures among elderly patients

BackgroundHip fractures following falls by the elderly, which increase with age, are increasing in number annually. The incidence of refracture (second hip fractures) has been reported to be 5%–10% in Japan and is expected to increase with the aging of the population in the future. Therefore, through a retrospective cohort study, we attempted to clarify the risk factors associated with second hip fractures.MethodsA total of 400 patients were consecutively treated for hip fracture at a single orthopedic hospital between January 2001 and December 2007. We excluded 16 subjects: 11 patients who died within a year after a hip fracture and 5 who were <50 years of age. The remaining 384 patients, consisting of 64 men and 320 women, were chosen as the study subjects. The mean age of the subjects at the time of the initial fracture was 83.1 ± 9.0 years (range 51–102 years). Age, sex, interval between the two fractures, body mass index (BMI), length of bed-rest periods and of rehabilitation periods, living place after an initial fracture, and complicating diseases were determined from medical records. Furthermore, effectors of second hip fractures were extracted using the Cox proportional hazard model.ResultsIn all, 384 patients were observed for 1140.0 person-years (mean: 3.0 ± 1.4 years per patient) following the initial hip fracture. During the observation period, 49 second hip fractures were identified, giving an overall incidence of 0.043 per person-year. The second fracture occurred within 3 years in 85.7% (42 patients). Dementia and respiratory disease were recognized as being significantly related to refracture. Using a Cox proportional hazard model, dementia showed a significant influence, with the hazard ratio (HR) 1.87 [95% confidence interval (CI) 1.02–3.41; P = 0.042]. Respiratory diseases also were associated with second hip fracture (HR 4.41, 95% CI 2.33–8.34; P < 0.001).ConclusionsIn this study, 85.7% of refractures occurred within 3 years of the first fracture, with dementia and respiratory disease being the complicating factors that influenced refracture.