Guideline-based Treatment of Glucocorticoid-induced Osteoporosis in Patients with Rheumatoid Arthritis: A Retrospective Study with the AORA Registry.

Glucocorticoid-induced osteoporosis (GIOP) is one of the side effects associated with glucocorticoid (GC) therapy. In 2014, the Japanese Society for Bone and Mineral Research (JSBMR) provided new guidelines for the management and treatment of GIOP. The aim of the present study was to clarify the prevalence of patients with rheumatoid arthritis (RA) requiring treatment according to the new guidelines and to identify risk factors associated with lack of treatment in these patients. Patients in the 2018 Akita Orthopedic group on Rheumatoid Arthritis (AORA) database were enrolled. Of 2,234 patients with RA in the database, 683 (30.6%) met the 2014 JSBMR guideline treatment criteria, and 480 (70.3%) had been treated. The untreated group included a larger number of males, younger patients, and patients treated in clinics rather than hospital (p<0.001, p=0.015, and p<0.001, respectively). Multivariate analyses found that male sex, younger age, and clinic-based RA care were significant risk factors associated with lack of treatment (p<0.001, p=0.013, and p<0.001, respectively). Thus, male sex, younger age, and clinic-based care were identified as risk factors.

Ultrasound-Guided Peripheral Nerve Blocks Performed by Orthopedic Surgeons: A Retrospective, Multicenter Study in Akita Prefecture, Japan.

The shortage of doctors is a societal problem, especially in rural areas such as Akita Prefecture, Japan. Therefore, it is not unusual in Akita for orthopedic surgeons to perform upper and lower limb surgeries under ultrasound-guided peripheral nerve blocks managed by the operators themselves. Multicenter studies of ultrasound-guided peripheral nerve blocks performed by orthopedic surgeons have not been reported. The purpose of this study was to clarify the safety and reliability of ultrasound-guided peripheral nerve blocks performed by orthopedic surgeons in Akita. A total of 1,674 upper extremity surgery cases operated under ultrasound-guided peripheral nerve blocks at 8 hospitals in Akita prefecture from April 2016 to April 2018 were investigated retrospectively. These blocks were performed by a total of 37 orthopedic surgeons, including senior surgeons and residents. In 321 of the 1,674 cases (19%), local anesthetics were added to the surgical field. Two cases with special factors were converted to general anesthesia. There were 2 cases of complications associated with the nerve block, but they were all transient and recovered promptly. The block site and the hospital where the block was performed showed a significant relationship with the addition of local anesthetics to the surgical site (P < 0.001). Surgery time, age at surgery, and surgical site showed no significant relationships with the addition of local anesthetics. The volume of the anesthetic used for the nerve block showed a significant inverse relationship with the addition of local anesthetics (P=0.040). Many orthopedic surgeons in Akita prefecture began to perform ultrasound-guided peripheral nerve blocks, which had a reliable anesthesia effect with no noticeable complications, whether performed by residents or senior orthopedic surgeons, and this is a useful anesthetic technique for orthopedic surgeons.

Combined treatment with minodronate and vitamin C increases bone mineral density and strength in vitamin C-deficient rats.

OBJECTIVES: Reduced bone quality caused by vitamin C deficiency in older persons may lead to incidental fragility fractures during bisphosphonate treatment, although bisphosphonate increases bone mineral density (BMD). This study aimed to evaluate the effects of minodronate and ascorbic acid (Aa) on BMD, bone quality, and bone strength in Aa-deficient osteogenic disorder Shionogi (ODS) rats. METHODS: Six-month-old ODS rats were divided into four groups (n = 20 per group): (1) Aa supplementation (Aa+); (2) Aa-deficient (Aa-); (3) Aa supplementation and minodronate administration (Aa+ + Mino); and (4) Aa-deficient and minodronate administration (Aa- + Mino). BMD, bone strength, bone histomorphometry, and bone quality determined using Fourier transform infrared spectroscopy imaging (FTIRI) were evaluated after 4 and 8 weeks. RESULTS: BMD was significantly higher in the Aa+ + Mino group than in the Aa- group (p < 0.05). Bone strength was significantly higher in the Aa+ and Aa+ + Mino groups than in the Aa- group (p < 0.05). Furthermore, bone strength was significantly higher in the Aa+ + Mino group than in the Aa- + Mino group (p < 0.05). Minodronate treatment irrespective of Aa supplementation significantly decreased bone resorption compared with the Aa+ and Aa- groups (p < 0.05). No significant differences in the parameters evaluated by FTIRI were observed between the groups. CONCLUSIONS: Aa supplementation improved bone strength in ODS rats. Combined treatment with minodronate and Aa, but not minodronate alone, improved bone strength and increased BMD. Aa is required for bone health because it is essential for osteoblast differentiation.

Healing of bisphosphonate-associated atypical femoral fractures in patients with osteoporosis: a comparison between treatment with and without teriparatide.

Atypical femoral fracture (AFF) often appears with bisphosphonate use. Teriparatide (TPTD) treatment may promote AFF healing, but few controlled or comparative studies have examined the effects of TPTD on healing of bisphosphonate-associated AFF. We retrospectively reviewed the medical records of 45 consecutive AFFs in 34 Japanese patients who had received oral bisphosphonates (alendronate or risedronate) for osteoporosis before AFF and had been followed for ≥12 months (range, 12-90 months). Thirty-seven complete or incomplete AFFs (82 %) were treated surgically and eight incomplete AFFs (18 %) were treated conservatively. Bisphosphonates were stopped at diagnosis. Based on TPTD use after fracture, AFFs were divided into non-TPTD (n = 24) and TPTD (n = 21) groups. Time to fracture-healing and frequency of delayed healing or non-union were compared between groups. Because fracture type (complete or incomplete) differed significantly between groups, only subanalyses for all surgically treated AFFs (complete and incomplete), surgically treated complete AFFs, and conservatively treated incomplete AFFs were performed. In subanalyses for all AFFs treated surgically, mean (± standard deviation) time to fracture healing was significantly better in the TPTD group (5.4 ± 1.5 months) than in the non-TPTD group (8.6 ± 4.7 months; P = 0.012), and the frequency of delayed healing or non-union was significantly lower in the TPTD group than in the non-TPTD group (P = 0.014). Subanalyses for surgically treated complete AFFs yielded similar results, but subanalyses for incomplete AFFs treated conservatively showed no significant differences between groups. TPTD treatment appears to significantly shorten the postoperative time to fracture healing and reduce rates of delayed healing or non-union after bisphosphonate-associated AFF.

Effects of combined therapy of alendronate and low-intensity pulsed ultrasound on metaphyseal bone repair after osteotomy in the proximal tibia of aged rats.

Bisphosphonates and low-intensity pulsed ultrasound (LIPUS) are both known to maintain or promote callus formation during diaphyseal fracture healing. However, the effect of these treatments on the repair of metaphyseal fractures has not been elucidated. To evaluate the effects of bisphosphonates and/or LIPUS on cancellous bone healing, an osteotomy was performed on the proximal tibial metaphysis of 9-month-old Sprague-Dawley rats (n = 64). Treatment with alendronate (1 µg/kg/day), LIPUS (20 min/day), or a combination of both was administered for 2 or 4 weeks, after which changes in bone mineral density (BMD), bone histomorphometric parameters, and the rate of cancellous bony bonding were measured. Alendronate suppressed bone resorption parameters at 2 weeks (p = 0.019) and increased bone volume and BMD at 4 weeks (p = 0.034 and p = 0.008, respectively), without affecting bony bonding. LIPUS had no significant effect on any of the histomorphometric parameters at 2 or 4 weeks, but significantly increased in BMD at 4 weeks (p = 0.026) as well as the percentage of bony bonding at both 2 and 4 weeks (p < 0.01). The combined therapy also showed significantly increased BMD compared with the control group at 4 weeks (p = 0.010) and showed a trend toward increased bony bonding. In conclusion, alendronate and LIPUS cause an additive increase in BMD at the affected metaphysis: alendronate increases the bone volume at the osteotomy site without interrupting metaphyseal repair, whereas LIPUS promotes metaphyseal bone repair, without affecting bone histomorphometric parameters.

Simultaneous dislocation of radiocapitellar and distal radioulnar joint.

A 45-year-old male presented to the emergency room of our institution complaining of severe pain around the left elbow. While playing volleyball, he slipped down with his left arm hit between the floor and his body. He complaind of strong pain from left elbow to hand, and active motion of elbow and wrist joint was impossible. His forearm was held in supinated position. On X-ray examination, radius head was deviated to anterior lateral side, and distal end of radius was dislocated to dorsal side. Tenderness was prominent at the site of radial head and distal radioulnar joint. Surgical treatment was performed using triceps tendon strip. Good functional recovery was gained.

Analgesic effects of minodronate on formalin-induced acute inflammatory pain in rats.

Minodronate is expected to produce greater analgesic effects than other bisphosphonates. However, there are no studies comparing bisphosphonate analgesic effects on formalin-induced acute inflammatory pain in rats. The purpose of the present study was to evaluate the analgesic effects of minodronate, morphine, and placebo. Four-month-old female Wistar rats were administered minodronate (50 mg/kg), morphine (10 mg/kg), or vehicle (n = 10 each) injections. Thirty minutes later, all rats were injected with formalin (right hind paw) to induce acute inflammatory pain. Paw licking and lifting as indicators of nociceptive pain responses were monitored from 0 to 5 min (phase 1; chemical-stimulation state) and then from 10 to 30 min (phase 2; spinal-sensitized state) after injection. The percentage of limb usage of the formalin-injected and the non-injected sides were measured in phases 1 and 2 by counting foot stamps. Minodronate significantly decreased nociceptive responses and increased limb usage compared with vehicle in phase 2 only (P < 0.05). Morphine significantly decreased nociceptive responses and increased limb usage compared with minodronate and vehicle in both phase 1 and 2 (P < 0.05). In conclusion, minodronate showed significant analgesic effects for formalin-induced acute pain in the spinal-sensitized state.

Intermittent administration of human parathyroid hormone before osteosynthesis stimulates cancellous bone union in ovariectomized rats.

It has been reported that intermittent administration of human parathyroid hormone (h-PTH) promotes bone healing after surgery for osteoporotic fractures. If bone healing is promoted by the administration of h-PTH during pre-operative waiting period, we can prevent prolonged bed rest. Therefore, we evaluated the effects of pre-operative h-PTH treatment on cancellous bone union and its mechanism for fracture healing in ovariectomized rats as a model for osteoporosis. Ovariectomized 7-month-old female Sprague-Dawley rats underwent an osteotomy of the proximal tibia as a fracture model, and h-PTH (30 µg/kg body weight) or vehicle was administered as a pre-operative treatment for one week. After the one-week treatment, tibiae were fixed with wire for osteosynthesis, and h-PTH or vehicle was administered for 1 or 3 weeks following wire fixation. In addition to bone histomorphometry, we used alcian blue/hematoxylin stained sections for evaluating cartilage volume and immunostained sections for analyzing the expression of proliferating cell nuclear antigen (PCNA) for cell proliferation and that of Sox9 and Runx2, differentiation markers for cartilage cells and osteoblasts, respectively. Pre-operative treatment with PTH significantly increased bone volume. Pre-operative and pre- to post-operative treatment with PTH for 2 weeks significantly promoted bone union. Pre-operative treatment with PTH significantly increased cartilage volume, and pre- to post-operative treatment with PTH for 2 weeks significantly increased the percentage of cells positive for Runx2 (p < 0.01), but not PCNA or Sox9. Pre-operative administration of h-PTH enhances bone union by promoting cartilage formation and cell differentiation to osteoblasts, but not by promoting cell proliferation.

Low serum levels of undercarboxylated osteocalcin in postmenopausal osteoporotic women receiving an inhibitor of bone resorption.

Osteocalcin, a bone-specific protein synthesized by osteoblasts, undergoes vitamin K-dependent gamma-carboxylation. Undercarboxylated osteocalcin (ucOC) represents inadequately carboxylated osteocalcin, and this fraction increases with vitamin K insufficiency. Alendronate is a bisphosphonate that inhibits bone resorption, thereby increasing bone mineral density (BMD), while also reducing bone formation closely coupled with bone resorption. The aim of this cross-sectional study was to evaluate the influence of alendronate on serum levels of ucOC, cross-linked N-telopeptide of type 1 collagen (NTx), a marker of bone resorption, and bone alkaline phosphatase (BAP), a marker of bone formation. Forty-six postmenopausal osteoporotic women were divided into three groups: patients receiving alendronate (5 mg/day or 35 mg/week) for >or= 6 months (n = 29) or < 6 months (n = 7), and patients receiving no medication related to bone metabolism (n = 10). Serum ucOC levels were significantly lower in patients with long-term treatment (p < 0.0001) or short-term treatment (p = 0.0223) than in untreated patients. Serum ucOC levels correlated positively with both BAP (r = 0.695, p < 0.0001) and NTx (r = 0.494, p = 0.0004) in all participants. Since low serum levels of BAP and NTx are associated with decreased levels of bone formation and bone resorption, respectively, these findings suggest that low serum ucOC levels may reflect the suppression of bone turnover. In conclusion, low serum ucOC levels reflect suppressed bone turnover and/or adequate levels of vitamin K in patients receiving an inhibitor of bone resorption.