Long-term oral bisphosphonates delay healing after tooth extraction: a single institutional prospective study.

Tooth extraction in patients receiving bisphosphonates is thought to be a risk factor for osteonecrosis of the jaw (ONJ); however, ONJ did not develop, even when tooth extraction was performed with continued oral bisphosphonate therapy. A drug holiday from bisphosphonates before tooth extraction may not be necessary. INTRODUCTION: It is controversial whether bisphosphonate withdrawal is necessary prior to invasive procedures such as tooth extraction in order to prevent bisphosphonate-related osteonecrosis of the jaw (BRONJ). This study aimed to evaluate the clinical safety of continuing oral bisphosphonate therapy in patients undergoing tooth extraction. METHODS: We prospectively enrolled 132 patients (20 men, 112 women) who were receiving oral bisphosphonates for the prevention or treatment of osteoporosis and required tooth extraction. All patients were managed using an identical protocol, which included preoperative antibiotic prophylaxis and did not necessarily require complete wound closure. The patients were classified into groups according to the duration of bisphosphonate administration: < 2 years (n = 51), 2-5 years (n = 41), 5-10 years (n = 28), and > 10 years (n = 12). The groups were compared regarding the time taken for the extraction socket to heal, and the occurrence of BRONJ. Follow-up duration was at least 3 months. RESULTS: A total of 274 teeth were removed. Long-term oral bisphosphonate therapy for > 5 years significantly delayed the healing of the extraction socket in comparison with administration for < 5 years; however, BRONJ did not develop in any group. There was no prolongation of wound healing due to systemic risk factors such as glucocorticoid administration and diabetes mellitus. There were no adverse skeletal events such as bone fracture. CONCLUSIONS: Patients who underwent tooth extraction with continued oral bisphosphonate therapy showed delayed healing of the extraction socket as the cumulative administration period prolonged, but BRONJ did not develop.

Usefulness of an accelerometer-based portable navigation system in total knee arthroplasty.

AIMS: The aim of this study was to evaluate the effects of using a portable, accelerometer-based surgical navigation system (KneeAlign2) in total knee arthroplasty (TKA) on the alignment of the femoral component, and blood loss. PATIENTS AND METHODS: A total of 241 consecutive patients with primary osteoarthritis of the knee were enrolled in this prospective, randomised controlled study. There were 207 women and 34 men. The mean age of the patients was 74.0 years (57 to 89). The KneeAlign2 system was used for distal femoral resection in 121 patients (KA2 group) and a conventional intramedullary femoral guide was used in 120 patients (IM group). RESULTS: One patient (0.8%) in the KA2 group and 19 in the IM group had an alignment which was > 3° away from the neutral mechanical axis (p < 0.01). The mean deviation from neutral alignment was 1.01° (standard deviation (sd) 1.0°) in the KA2 group and 1.93° (sd 1.7°) in the IM group (p < 0.01). Blood loss was significantly less in the KA2 group compared with the IM group (784 ml (sd 357) versus 1071 ml (sd 310), p < 0.001). CONCLUSION: The KneeAlign2 system provides a technically straightforward method for identifying the femoral head and performing an accurate distal femoral resection at TKA with significantly less blood loss compared with a conventional intramedullary guide. Cite this article: Bone Joint J 2017;99-B:1047-52.

Time to onset of bisphosphonate-related osteonecrosis of the jaws: a multicentre retrospective cohort study.

OBJECTIVES: Osteonecrosis of the jaw (ONJ) is a potentially severe adverse effect of bisphosphonates (BP). Although the risk of ONJ increases with increasing duration of BP treatment, there are currently no reliable estimates of the ONJ time to onset (TTO). The objective of this study was to estimate the TTO and associated risk factors in BP-treated patients. SUBJECTS AND METHODS: Retrospective analysis of data from 22 secondary care centres in seven countries relevant to 349 patients who developed BP-related ONJ between 2004 and 2012. RESULTS: The median (95%CI) TTO was 6.0 years in patients treated with alendronate (n = 88) and 2.2 years in those treated with zoledronate (n = 218). Multivariable Cox regression showed that dentoalveolar surgery was inversely associated, and the use of antiangiogenics directly associated, with the TTO in patients with cancer treated with zoledronate. CONCLUSIONS: The incidence of ONJ increases with the duration of BP therapy, with notable differences observed with respect to BP type and potency, route of administration and underlying disease. When data are stratified by BP type, a time of 6.0 and 2.2 years of oral alendronate and intravenous zoledronate therapy, respectively, is required for 50% of patients to develop ONJ. After stratification by disease, a time of 5.3 and 2.2 years of BP therapy is required for 50% of patients with osteoporosis and cancer, respectively, to develop ONJ. These findings have significant implications for the design of future clinical studies and the development of risk-reduction strategies aimed at either assessing or modulating the risk of ONJ associated with BP.

Spectrum of clinical and genetic features of patients with inherited platelet disorder with suspected predisposition to hematological malignancies: a nationwide survey in Japan.

BACKGROUND: Inherited thrombocytopenia (IT) contains several forms of familial thrombocytopenia and some of them have propensity to hematological malignancies. The etiological and genetic features of this heterogeneous syndrome have not yet been elucidated. PATIENTS AND METHODS: We conducted a nationwide survey to collect clinical information and samples from patients with familial thrombocytopenia and/or hematological malignancies in order to obtain a comprehensive understanding of IT. RESULTS: Among the 43 pedigrees with clinical samples, RUNX1 mutations were identified in 8 pedigrees (18.6%). While MYH9 and ANKRD26 mutations were identified in 2 and 1 pedigrees, respectively, no gene mutations were detected in the remaining 32 pedigrees from a panel of previously reported pathogenetic mutations. Clinical data were comparable between FPD/AML and non-FPD/AML probands. CONCLUSIONS: Our study clarified that it is unexpectedly difficult to diagnose FPD/AML based on clinical information alone, and thus, genetic testing is strongly recommended. Our survey also identified some pedigrees with a strong family history of myelodysplastic syndromes of unknown origin. Additionally, there were 14 pedigrees in which three or more members were affected by immune thrombocytopenia (ITP), and a computer-aided simulation suggested that such a distribution almost never happens by coincidence, which implicates a genetic predisposition to ITP.

Impaired immune response to voluntary arm-crank ergometer exercise in patients with cervical spinal cord injury.

STUDY DESIGN: Non-randomized study. OBJECTIVE: The mechanism underlying exercise-induced argumentation of natural killer cell cytotoxic activity (NKCA) in humans remains unclear. To address this, NKCA responses were studied during and after exercise in persons with cervical spinal cord injury (CSCI) and dysfunctional sympathetic nervous system. SETTING: Kibikogen Rehabilitation Center for Employment Injuries. METHODS: We examined the NKCA responses to 20-min arm-crank ergometer exercise at 60% of maximum oxygen consumption in eight persons with CSCI (between C6 and C7) and six able-bodied subjects. NKCA, adrenaline, and cortisol were measured before, immediately after exercise, 1 h after exercise, and 2 h after exercise. RESULTS: In able-bodied subjects, NKCA increased immediately after exercise (P<0.01) and then decreased to below the pre-exercise level 1 h after exercise, before recovering to the baseline level at 2 h after exercise. Plasma adrenaline concentrations increased significantly immediately after exercise (P<0.01) and returned to the baseline level 1 h after exercise. The plasma cortisol level did not change throughout the study. In contrast, NKCA, plasma concentrations of adrenaline, and cortisol did not change throughout the study in subjects with CSCI. CONCLUSION: In subjects with CSCI, the lack of response in NKCA throughout the experiment is probably mainly due to a dysfunctional sympathetic nervous system.

The incidence of the patellar clunk syndrome in a recently designed mobile-bearing posteriorly stabilised total knee replacement.

The patellar clunk syndrome describes painful catching, grinding or jumping of the patella when the knee moves from a flexed to an extended position after total knee replacement (TKR). The posterior stabilised TKR had been noted to have a higher incidence of this problem. Mobile-bearing posteriorly stabilised TKRs have been introduced to improve patellar tracking and related problems by a mechanism of self-alignment. We evaluated the patellar clunk syndrome in 113 knees in 93 patients with such a TKR at a mean follow-up of 2.3 years (2.0 to 3.2). The syndrome was identified in 15 knees (13.3%). Logistic regression analysis showed that the absolute value of the post-operative angle of patellar tilt was significantly associated with the occurrence of patellar clunk (p = 0.025). Patellar tracking should be carefully checked during surgery.

External hip protectors are effective for the elderly with higher-than-average risk factors for hip fractures.

UNLABELLED: In our cluster randomised controlled trial for efficacy of hip protector with 672 ambulatory elderly women, a hip protector was more effective for prevention of hip fractures in residents with fall history (n = 202; hazard ratio (HR), 0.375; 95%CI, 0.14-0.98; p = 0.05) and body-mass index (BMI) < or = 19.0 (n = 206; HR, 0.37; 95%CI, 0.14-0.95; p = 0.04) by a Cox proportional hazards regression model. INTRODUCTION: Hip fractures result from both osteoporosis and falling. A potentially cost-effective method of preventing hip fractures involves the use of hip protectors but recent studies have revealed the uncertain effectiveness of hip protectors even in institutional settings. METHODS: This study was a cluster randomised controlled trial with nursing homes. We randomly assigned 76 homes with 672 ambulatory but frail elderly women. Several risk factors were assessed at baseline and incorporated into a Cox proportional hazards regression model. UMIN Clinical Trials Registry number is UMIN000000467. Research period was between January 2004 and March 2006. RESULTS: In the intervention group, 19 hip fractures occurred (54.0/1,000 person-years), whereas 39 hip fractures occurred in the control group (78.8/1,000 person-years). Hazard ratio of hip fracture in the intervention group was 0.56 (95%CI, 0.31-1.03; p = 0.06) after adjusting for risk factors. In subgroup analysis, hip protectors were more effective for prevention of hip fractures in residents with fall history (n = 202; HR, 0.375; 95%CI, 0.14-0.98; p = 0.05) and BMI < or = 19.0 (n = 206; HR, 0.37; 95%CI, 0.14-0.95; p = 0.04). Overall compliance with use of hip protectors was 79.7%. CONCLUSION: Risk of hip fracture can be reduced by hip protectors among elderly women with fall history and low BMI.

Effect of daily oral minodronate on vertebral fractures in Japanese postmenopausal women with established osteoporosis: a randomized placebo-controlled double-blind study.

UNLABELLED: SUMMARY; A randomized placebo-controlled trial was conducted to examine the effect of daily oral 1 mg minodronate on vertebral fractures in 704 postmenopausal women with established osteoporosis for 24 months. Minodronate treatment reduced vertebral fractures by 59% without serious adverse events. Minodronate is a safe and effective bisphosphonate for osteoporosis treatment. INTRODUCTION: Minodronate increases bone mineral density (BMD) in postmenopausal osteoporotic patients. However, its efficacy in reducing osteoporotic fractures has not been tested. METHODS: To examine anti-fracture efficacy and safety of daily oral minodronate in postmenopausal women with established osteoporosis, a randomized, double-blind, placebo-controlled trial was conducted in 704 postmenopausal women (55 to 80 years) with one to five vertebral fractures and low BMD. Subjects were randomly assigned to receive daily oral 1 mg minodronate (n = 359) or placebo (n = 345) for 24 months, with daily supplements of 600 mg calcium and 200 IU vitamin D(3). RESULTS: Daily 1 mg minodronate for 24 months reduced the risk of vertebral fractures by 59% (95% CI, 36.6-73.3%). Furthermore, when fractures during the first 6 months were eliminated, the risk of vertebral fractures from 6 to 24 months was reduced by 74% in minodronate-treated group. Minodronate treatment also reduced height loss. Bone turnover markers were suppressed by about 50% after 6 months of minodronate treatment and remained suppressed thereafter. The overall safety profile including gastrointestinal safety was similar between the two groups. CONCLUSIONS: Daily oral minodronate is safe, well-tolerated, and is effective in reducing vertebral fracture risk in postmenopausal women with established osteoporosis.

Serum keratan sulfate is a promising marker of early articular cartilage breakdown.

OBJECTIVES: To find serum markers that may serve as indices for an early diagnosis of degeneration or damage of the articular cartilage. METHODS: Twenty-four healthy volunteers, 19 individuals with knee trauma (KT) and 31 with knee osteoarthritis (OA) were evaluated. KT patients were divided into a group (n = 5) with an injury <2 months old (recent KT) and a group (n = 14) with that >2 months old (old KT). Articular cartilage damage was assessed using either arthroscopy or direct observation. Serum concentrations of hyaluronic acid (HA), cartilage proteoglycan aggrecan turnover epitope (CS846) and cartilage oligomeric protein (COMP) were measured using enzyme-linked immunosorbent assay kits and those of keratan sulfate (KS) and chondroitin-6-sulfate (C6S) using high-performance liquid chromatography. RESULTS: Serum KS in the recent KT group (2095 +/- 594 ng/ml) was significantly higher than that in the old KT group (1373 +/- 418 ng/ml; P = 0.021), and serum COMP in the recent KT group (1572 +/- 182 ng/ml) showed a tendency that was higher than that in the old KT group (1350 +/- 250 ng/ml; P = 0.079). Serum KS in OA patients with Kellgren and Lawrence (KL) grades 0 and I (1456 +/- 334 ng/ml) showed a tendency that was higher than that in OA patients with KL grades II, III and IV (1248 +/- 220 ng/ml; P = 0.084). CONCLUSIONS: The serum concentration of KS correlated with the damage of the articular cartilage and it was significantly increased even at an early stage after the injury.

Proteinase-activated receptors in the gastrointestinal system: a functional linkage to prostanoids.

Proteinase-activated receptors (PARs), G protein-coupled receptors, play critical roles in the alimentary system. Increasing evidence suggests that endogenous prostaglandins (PGs) mediate some of PARs' gastrointestinal functions. Systemic administration of the PAR1 agonist protects against gastric mucosal injury through PG formation in rats. PGs also appear to contribute, at least in part, to enhancement of gastric mucosal blood flow and suppression of gastric acid secretion by PAR1 activation. There is also evidence for involvement of PGs in modulation of gastrointestinal motility by PAR1 or PAR2. Importantly, modulation of ion transport by PAR1 or PAR2 in the intestinal mucosal epithelium is largely mediated by PGs. Studies using gastric and intestinal mucosal epithelial cell lines imply that the PAR1-triggered formation of PGs involves multiple signaling pathways including Src, EGF receptor trans-activation and activation of MAP kinases. Collectively, a functional linkage of PAR1 and/or PAR2 to PGs is considered important in the gastrointestinal system.

Clinical outcome of extrasynovial steroid injection for trigger finger.

A prospective clinical study was performed to investigate the clinical results of extrasynovial (subcutaneous) steroid injection for trigger finger. One hundred and twenty-nine trigger fingers were investigated in 100 adult patients; 76 were women and 24 were men. Their mean age was 60 years (range: 17 to 88 years). We classified trigger fingers into three different grades according to clinical severity at a medical examination. All patients were injected with betamethasone mixed with lidocaine. Surgical release of the A1 pulley was performed at the patients' request if steroid injection therapy was not effective. Pain and snapping were relieved in 98% and 74% of cases, respectively. Recurrence occurred in about half our patients, but the same clinical benefit was obtained after re-injection. Surgery was performed for seven fingers. No complications of steroid injections were observed. This study suggests that extrasynovial steroid injection is a valuable conservative treatment for trigger finger and it is not necessary to try and inject into the tendon sheath to get a good result and markedly reduce the risk of causing damage to tendons and other structures.

Evaluation of the flexion gap by axial radiography of the distal femur.

The shape of the flexion gap in 20 normal knees was evaluated by axial radiography of the distal femur, and the results compared with those obtained in a previous study by MRI. The observed asymmetry was reduced by 29% using radiography, with a mean value of 3.6 degrees (1.5 degrees to 6.3 degrees) compared with that obtained by MRI of 5.1 degrees (2.6 degrees to 9.5 degrees), a mean discrepancy of 1.49 degrees. The results obtained by radiography and MRI showed a strong correlation (r = 0.78). Axial radiography is acceptable for the evaluation of the flexion gap and is less expensive and more comfortable to perform than MRI. Additionally, no metallic artefact occurs when the radiological method is used for assessment after arthroplasty.

A case of toe macrodactyly treated by application of a vascularised nail graft.

Macrodactyly is a relatively rare congenital abnormality of the fingers and toes and is difficult to treat. We report a new method for treating toe macrodactyly in which a nail with a vascularised pedicle is raised, the toe is shortened to an appropriate length, and the nail transferred to an aesthetically appropriate proximal site. Although this technique is of a higher level of difficulty than conventional procedures involving pedicled nail flaps, allows aesthetically more favourable nail reconstruction by single-stage operation.

Synthetic biodegradable polymers as drug delivery systems for bone morphogenetic proteins.

Bone morphogenetic proteins (BMP) induce bone formation in vivo, and clinical application in repair of bone fractures and defects is expected. However, appropriate systems to deliver BMP for clinical use need to be developed. We synthesized a new synthetic biodegradable polymer, poly-D,L-lactic acid-para-dioxanone-polyethylene glycol block copolymer (PLA-DX-PEG), to serve as a biocompatible, biodegradable polymer for recombinant human (rh) BMP-2 delivery systems. In animal experiments, new bone was efficiently formed and a large bone defect was repaired using PLA-DX-PEG/rhBMP-2 composites. In addition, this new polymer could be used as an injectable delivery system for rhBMP-2. The rhBMP-2/PLA-DX-PEG composites also could be combined with other materials such as hydroxyapatite or titanium. This new synthetic polymer might be used for rhBMP-2 delivery in various clinical situations involving repair of bone, leading to great changes in orthopedic treatment.

The flexion gap in normal knees. An MRI study.

Varus and valgus joint laxity of the normal living knee in flexion was assessed using MRI. Twenty knees were flexed to 90 degrees and were imaged in neutral and under a varus-valgus stress in an open MRI system. The configuration of the tibiofemoral joint gap was studied in slices which crossed the epicondyles of the femur. When a varus stress was applied, the lateral joint gap opened by 6.7 +/- 1.9 mm (mean +/- SD; 2.1 to 9.2) whereas the medial joint gap opened by only by a mean of 2.1 +/- 1.1 mm (0.2 to 4.2). These discrepancies indicate that the tibiofemoral flexion gap in the normal knee is not rectangular and that the lateral joint gap is significantly lax. These results may be useful for adequate soft-tissue balancing and bone resection in total knee arthroplasty and reconstruction surgery on ligaments.

[Solitary hemangioma of the rib; report of a case].

A case of solitary hemangioma which occurred in the rib. Tumor located in the right seventh rib, incidentally taken X-ray film demonstrated bone tumor, but she had no symptoms. Four years after, chest pain occurred and taken X-ray film, tumor size was inceeced. Computed tomography (CT) showed an expansile, well demarcated lesion, with thin corices and fine trabeclae. Chest wall, from the sixth rib to the eighth rib resection was performed and surgical margin was 4 cm. This case were diagnosed hemangioma of the rib. Hemangiomas of the bone are rare benign vascular tumors that account for less than 1% of all bony neoplasms. These lesions are most often occurring in the vertebral column or in the skull. The localization to the ribs is even more rare, with only sporadic case reports in the literature.

A case of mucopolysaccharidosis IV with lower leg paresis due to thoraco-lumbar kyphoscoliosis.

We treated a patient of type IV mucopolysaccharidosis (Morquio's disease) with lower leg paresis due to kyphoscoliosis. A 65-year-old woman presented with Morquio's disease. A lateral radiograph demonstrated the classic bullet-shaped vertebrae and a 65 degrees thoraco-lumbar kyphosis. After the age of 60, she suffered from numbness in both lower legs and walking disturbance. Bilateral patellae-tendon reflexes were exaggerated. MRI showed compression of the spinal cord around T12 to L2 with a highlighted area of change inside the spinal cord. Myelography and computed tomography after the myelography showed narrowing of the sub-arachnoidal space and deformation of the spinal cord around the T12 to L2 levels. Severe vertebral osteoporosis made it necessary to first perform posterior correction of the kyphosis and fusion. The curve was stabilised with the Luque method from T7 to L4. Her neurological condition markedly recovered, but 1 year after surgery her neurological condition again began to deteriorate, resulting in walking disturbance. For this reason, anterior decompression and fusion through a lateral thoracotomy was undertaken. Decompression of the spinal cord and a bone graft from the iliac crest were attained. The patient's neurological condition again improved, but not as much as immediately after the first operation.