Correction to: Effectiveness of monthly intravenous ibandronate on the low responders to oral bisphosphonate: the MOVEMENT study.

In the original publication of the article, the Figures 2 and 3 were published incorrectly. The corrected figures are given below.

Effectiveness of monthly intravenous ibandronate on the low responders to oral bisphosphonate: the MOVEMENT study.

The MOVEMENT study was designed to assess the effectiveness of monthly intravenous ibandronate on bone mineral density (BMD) in daily clinical practice in Japanese patients with primary osteoporosis whose lumbar spine BMD did not increase despite oral bisphosphonate therapy. This study was a multicenter, prospective, interventional study (52 sites; August 2015 to March 2018). Patients aged ≥ 50 years with primary osteoporosis, evaluated as low responders to oral bisphosphonate treatment for 1-3 years, continued on their existing oral bisphosphonate or switched to monthly intravenous ibandronate (1 mg) for 12 months. The primary endpoint was change in lumbar spine BMD from baseline to 12 months in the intravenous ibandronate group (IV IBN). A total of 240 and 141 patients were enrolled in the IV IBN and oral bisphosphonate groups (OBP), respectively. At 12 months, a significant increase in mean percent change from baseline in lumbar spine BMD was observed in the IV IBN (2.70%). This change was also significant at 6 months (1.92%). Similarly, the change in total hip BMD showed a significant increase at 12 months (0.78%). In the IV IBN, the responder rate, percentage of patient whose change from baseline of lumbar spine BMD has greater than 0%, for lumbar spine BMD was high at both 6 (72.3%, 141/195 patients) and 12 (78.0%, 145/186 patients) months. No new safety concerns were observed in either treatment group. Treatment with intravenous ibandronate significantly increased lumbar spine BMD without any new safety concerns in Japanese patients with osteoporosis who showed low response to existing oral bisphosphonates.

Treatment with once-weekly alendronate oral jelly compared with once-weekly alendronate oral tablet for Japanese patients with primary osteoporosis: An open-label, prospective, observational study.

BACKGROUND AND AIMS: Clinical data regarding alendronate jelly are limited. We compared the efficacy and safety of once-weekly alendronate oral jelly with once-weekly alendronate tablet formulations in the context of primary osteoporosis. METHODS: In this 6-month, open-label, prospective, observational study, Japanese patients aged ≥60 years with primary osteoporosis were included from 14 primary care centres in Japan. The effects of once-weekly alendronate oral jelly and tablet formulations on bone mineral density (BMD), bone turnover markers, and quality of life related to gastrointestinal symptoms were assessed at baseline and 6 months. Treatment was allocated by patient preference. This potentially confounding factor was adjusted for statistically. RESULTS: In total, 170 patients were enrolled (jelly, n = 97; tablet, n = 73). Mean percent changes in radius, lumbar spine, femoral neck, and hip BMD were similar in both treatment groups at 6 months. Both formulations decreased tartrate-resistant acid phosphatase 5b (TRACP-5b) and procollagen 1 N-terminal peptide (P1NP) between baseline and 6 months (by about 50% and 60%, respectively); no significant differences in mean changes were noted in these markers between groups. At 6 months, no significant differences were noted in visual analogue scale or EuroQOL five-dimension questionnaire scores between groups. The jelly group had significantly lower scores than the tablet group in the Izumo scale domains of heartburn (-0.81, P = 0.0040), epigastralgia (-0.94, P = 0.0003), and epigastric fullness (-0.49, P = 0.044). During treatment, more patients discontinued for upper gastrointestinal symptoms in the tablet group (n = 4) than the jelly group (n = 1). CONCLUSIONS: Once-weekly alendronate oral jelly 35 mg may be a suitable alternative therapeutic agent for primary osteoporosis in Japan.

[Acute phase reaction following bisphosphonates.]

Bisphosphonates are effective in decreasing bone resorption, the incidence of fragility fracure, and pain from bone metastases. Although relatively well tolerated, the initial dose(s)of intravenous or oral monthly aminobisphosphonates can be associated with an acute phase response, a nonspecific physiologic reaction associated with increased levels of inflammatory cytokines, fever, and flu like symptoms including fatigue, nausea, and myalgia within 3 days of dosing and lasting 7 days or less. Nitrogen-BPs(N-BPs)inhibit osteoclast function by acting as potent inhibitors of the enzyme farnesyl diphosphate(FPP)synthase in the mevalonate biosynthetic pathway. Following an intravenous infusion or oral monthly BPs, transient uptake of N-BP into peripheral blood monocytes results in intracellular accumulation of isopentenyl diphosphate(IPP)due to FPP synthase inhibition. Recognition of IPP by γδT cells triggers their activation and expansion, resulting in the release of pro-inflammatory cytokines that cause the flulike symptoms of the acute phase reaction. There is trial evidence that its severity can be reduced by more than half with coadministration of acetaminophen, so the short-term use of these drugs to lessen the APR is advisable in patients receiving their first dosing of N-BPs. Levels of 25(OH)D were negatively correlated with the incidence and severity of APR. Vitamin D reduces the intensity of musculoskeletal pain after dosing of N-BPs for postmenopausal osteoporosis. APR has minimal impact on long-term adherence to therapy. It is less common in subjects who have previously used bisphosphonates. Information of APR to a patient is important before administration.

15-year comparison of cementless total hip arthroplasty with anatomical or high cup placement for Crowe I to III hip dysplasia.

This study compared radiological and clinical results of Mallory-Head (Biomet, Warsaw, Indiana) cementless total hip arthroplasty (THA) by anatomical (AP group) or high cup placement (HP group) for Crowe I to III developmental dysplasia of the hip. Of the 68 hips studied, 43 hips were available for 15.3-year follow-up. Ten cups were placed at anatomical center with bulk bone grafting, and 33 cups were at high hip center without bulk bone grafting. No acetabular or femoral components showed loosening in either group. One standard polyethylene liner in a highly placed cup was revised due to excessive wear after 11 years. The average rate of polyethylene wear was 0.128 mm/year in the AP group and 0.148 mm/year in the HP group (except for the revision case). The extent of grafted bone coverage was 34.6% in the AP group. Hip center height was 24.5 mm from the inter-teardrop line in the HP group. The center of the hip horizontal location in the AP group (24.5 mm) and HP group (26.4 mm) was significantly shorter than in normal hips (35.6 mm). Postoperative center-edge angle was 11° (except grafted bone) in the AP group and 25° in the HP group. Mean Harris Hip Score in the AP group improved from 38 points preoperatively to 82 points postoperatively and in the HP group improved from 40 points preoperatively to 88 points postoperatively. Survivorship was 100% in the AP group and 97% in the HP group. Our results indicate that moderate high cup placement without bulk bone grafting at a horizontal locus more medial than that of a normal hip is an alternative durable solution.

[Disorder of bone quality in Paget's disease].

Paget's disease is a localized and progressive disorder of bone, characterized by increased bone remodeling. The increase of bone turnover changed bone quality in Paget's disease. The assessment of bone quality is consisted on two properties of structure and material. Bone quality is evaluated clinically by the bone turnover. Treatment of bisphosphonate in Paget's disease controlled bone turnover. There's a possibility that treatment of bisphosphonate improve not only the property of structure but also that of material. It's hoped that the newer and stronger bisphosphonates play an increasingly important role in the treatment for bone quality of Paget's disease.

Effects of 1,25(OH)2D3 on turnover, mineralization, and strength of bone in growing rats with liver cirrhosis induced by administration of carbon tetrachloride.

To clarify the effects of 1 alpha,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) on bone growth, strength, and turnover in growing rats with liver cirrhosis induced by carbon tetrachloride (CCl(4)) injection, groups of 4-week-old male Wistar rats (n = 10, each) were injected intraperitoneally with CCl(4) twice weekly for 7 weeks. One group was treated with the vehicle alone (Group 1). Three CCl(4)-injected groups were orally administered 1,25(OH)(2)D(3) at doses of 0, 0.05, and 0.1 micro g/kg, respectively (Groups 2, 3, and 4). At the end, serum levels of 1,25(OH)(2)D(3), IGF-I, and osteocalcin were reduced in Group 2 compared to Group 1, and the corresponding values in Group 4 were larger than those in Group 2. Urinary deoxypyridinoline levels increased in Group 2 compared to Group 1, and did not significantly differ in Groups 2-4. The values for bone sizes, mineral content (BMC) in the lumbar vertebra and femur, and ultimate bending load in the femur were reduced in Group 2 compared to Group 1, and lumbar BMC in Group 3 and bone sizes in Group 4 were larger than those in Group 2. The values for lumbar trabecular bone volume in Group 2 were reduced compared to Group 1, and the corresponding values in Group 4 were larger than those in Group 2. Bone formation rates, reduced in Group 2 compared to Group 1, did not differ in Groups 2-4. Parameters for trabecular osteoclasts did not differ among all groups. In the proximal tibia, the value of activation frequency (Ac.f) in Group 2 significantly decreased compared to Group 1. Ac.f values in Groups 3 and 4 were larger than that in Group 2. These data demonstrated that retardation of bone growth in CCl(4)-injected rats was associated with reduced serum 1,25(OH)(2)D(3) and IGF-I levels. The trabecular bone in the rats exhibited low turnover osteopenia. 1,25(OH)(2)D(3) administration partially prevented the growth disturbance, but did not substantially affect bone turnover. Factors other than 1,25(OH)(2)D(3) and IGF-I appeared to be critical in the low turnover osteopenia evident in liver cirrhosis.

[Pathophysiology, diagnosis and treatment of osteoporosis].

Patients with rheumatoid arthritis (RA) develop both generalized and periarticular osteoporosis. Osteoporosis in RA causes by increase of bone resorption, however the decrease of bone formation has been concerned in development of osteoporosis. Drug therapy have to bigin as early as osteopenia, and a potent inhibitor of bone resorption will be effective to suppress the increse of bone resorption in RA patients. RA-associated osteoporosis including grucocorticoid induced osteoporosis decreases bone formation, vitamin D and parathyroid hormon would become the useful drug for promoting the bone formation by examination of new agents, method and dosage of treatment for osteoporosis in RA patients.

Role of inducible nitric oxide synthase in skeletal adaptation to acute increases in mechanical loading.

To clarify the role of nitric oxide (NO) in regulation of bone metabolism in response to skeletal loading, we examined inducible NO synthase (iNOS) gene knockout mice in the tail-suspension model. Histomorphometric analyses of proximal tibias revealed that 7 days of tail suspension decreased the bone volume (BV/TV) and bone formation rate (BFR/BS) and increased the osteoclast surface (Oc.S/BS) in mice with all iNOS genotypes. Both iNOS+/+ and iNOS+/- mice responded to subsequent 14-day reloading, with increases in BV/TV and BFR/BS and a decrease in Oc.S/BS, whereas these responses were abolished in iNOS-/- mice. The osteoblasts flattened after tail suspension appeared cuboidal during subsequent reloading. Immunoreactivity for iNOS was detected in these osteoblasts and osteocytes by immunohistochemistry. These defective responses after reloading were rescued in iNOS-/- mice by treatment with an NO donor nitroglycerine (NG). Conversely, the responses in iNOS+/+ mice were inhibited by treatment with an NOS inhibitor aminoguanidine (AG). In bone marrow cell cultures, mineralized nodules derived from iNOS-/- mice after reloading were significantly reduced. Taken together, our results suggest that NO generated by iNOS in osteoblasts plays a critical role in adjusting bone turnover and increasing osteogenic activity in response to the acute increase in mechanical loading after tail suspension.