Disturbance of osteonal bone remodeling and high tensile stresses on the lateral cortex in atypical femoral fracture after long-term treatment with Risedronate and Alfacalcidol for osteoporosis.

An 83 year-old Japanese woman complained of left lateral thigh pain following a low-energy fall 4 months prior to admission. She had been treated for osteoporosis with Risedronate and Alfacalcidol for the previous five years. She was diagnosed with an atypical femoral fracture (AFF) according to the American Society for Bone and Mineral Research (ASBMR) Task Force revised criteria. Radiographs revealed cortical thickening and a transverse radiolucent fracture line in the lateral cortex of the shaft. MRI showed a high intensity signal on the T2WI image 1 cm long in the lateral cortex. The patient had normal levels of bone resorption and formation biomarkers except for low 25(OH) Vitamin D. Double fluorescent labeling was done preoperatively. Due to significant bowing, a corrective osteotomy and intramedullary nailing were performed, and the resected bone wedge was analyzed by bone histomorphometry. Three ground sections of the lateral cortex at the fracture site showed many and large pores, with or without tetracycline labeling. Histomorphometric assessment was done on intracortical pores, classified by a novel criteria, only to assess size of the pores to know prolonged osteoclastic activity and its characteristics of inner surfaces to assess whether bone formation has been occurring or not in labeling period in remodeling cycle, and coalition of multi-pores. Increased size with widespread variation of pores suggested prolonged osteoclastic activity in the reversal/resorptive phase. Bone labeling showed lamellar bone on the endocortical surface. We hypothesize that the case had developed from a regional disturbance of osteonal remodeling in the lateral cortex, in which accumulated microcracks might have initiated a resorption process resulting in resorption cavities, i.e., pores, which became larger due to prolonged activity of secondary osteoclasts. Various sized pores could form lamellar bone, still forming at the time of biopsy, some had formed lamellar bone, but stopped to form before labeling and not to start to form at all, probably due to incomplete coupling. Endocortical lamellar bone might had started to resorbed to smooth off endocortical surface, followed by formation of lamellar bone. The endocortical bone formation was assessed and its formation period is about 2.7 years. A finite element analysis using preoperative CT data revealed high tensile stresses on the lateral aspect of the femur. Histomorphometric results suggest that there might be more pores in the tensile area than the compressive area. These findings may subsequently connect accumulation of microcracks, an increase of size and number of pores and coalition and subsequent fracture in the lateral cortex.

Long-term outcomes of metacarpal fractures surgically treated using bioabsorbable plates: a retrospective study.

BACKGROUND: Implants made from bioabsorbable unsintered hydroxyapatite and poly-L-lactate composites (u-HA/PLLA) are widely used in the oral, maxillofacial, and orthopedic fields. This study assess the long-term (> 5 years) outcomes of patients with metacarpal fractures who were surgically treated using bioabsorbable plates and screws (Super-Fixsorb MX40 mesh; Teijin Medical Technology, Osaka, Japan). METHODS: A retrospective analysis of six patients with eight metacarpal fractures treated with bioabsorbable plates was done. All patients were followed for more than 5 years post-surgery. The clinical outcomes were evaluated using Q-DASH scores and the grip strength (GS): opposite side ratio. The resorption status of implants was assessed on plain computed tomography (CT) scans at final follow-up appointments. RESULTS: The mean age of the patients at the time of surgery was 29.5 years (16-54), and the median follow-up period was 81.8 months (68-101). All fractures united without displacement after an average of 3.5 months, and there were no implant specific complications associated with the use of absorbable plates. The mean grip strength ratio was 85.1% (56.8-104.5). The mean Q-DASH scores of 11.36 points (0-34.09) was good in all but two patients. We also observed that it took more than 8 years for the plates to be absorbed completely. CONCLUSIONS: This study demonstrates that the process of bioabsorption in metacarpal fractures might be completed in about 8 years, and the absorption speeds were different inside and outside of the bone. The bioabsorbable plates are more cost-effective than metallic implants. The potential for bioabsorbable plates to be used in various clinical procedures is promising.

Four-corner fusion method using a bioabsorbable plate for scapholunate advanced collapse and scaphoid nonunion advanced collapse wrists: a case series study.

BACKGROUND: Scaphoid excision and four-corner arthrodesis is an acceptable salvage procedure for the treatment of scapholunate advanced collapse (SLAC) and scaphoid nonunion advanced collapse (SNAC) wrists, since first popularized in the 1980s. We investigated the potential application of novel bioabsorbable plates and screws made of un-sintered hydroxyapatite/poly-L-lactide composite for the treatment of metacarpal fractures. We used this material for the fixation of four-corner fusions for SLAC or SNAC wrists commencing from April 2009. The purpose of this study was to clarify the controversy in the literature regarding the use of these plates. METHODS: The surgical procedures and clinical outcomes of four-corner fusions using a bioabsorbable (poly-L-lactic acid and hydroxyapatite) plate were reported. Ten patients (mean age, 59.2 years) with SLAC or SNAC wrists underwent fusions between April 2009 and June 2016. The primary diseases were scapholunate ligament injury, Preiser disease, and scaphoid pseudarthrosis. The mean postoperative follow-up period was 45.9 months (range, 12-86). RESULTS: In all patients, bone union was achieved without dislocation or pain. The mean wrist flexion and extension arc improved from 78.5 degrees before surgery to 90.5 degrees after surgery. Mean grip strength improved from 51 to 69% after surgery, and the Quick Disabilities of the Arm, Shoulder, and Hand (QuickDASH) score improved from 53.5 to 14.3. No complications such as infection, avascular swelling, or tendon adhesion were observed. This implant requires no removal of internal fixation devices, produces stable outcomes, and is an effective fusion technique. CONCLUSIONS: We summarized the outcomes of four-corner arthrodesis using bioabsorbable plates. Satisfactory clinical results were shown, with no obvious complications. This novel plate also serves as a good alternative for patients who are allergic to metals. Furthermore, bioabsorbable plates are advantageous as they do not require removal.

Disruption of the aldehyde dehydrogenase 2 gene increases the bone anabolic response to intermittent PTH treatment in an ovariectomized mouse model.

Aldehyde dehydrogenase 2 (ALDH2) is the enzyme that oxidizes the acetaldehyde produced by alcohol metabolism. This variant not only affects the response to alcohol but is also associated with several diseases, such as esophageal cancer, myocardial infarction, and particularly osteoporosis. In our previous study, we reported that compared to wild-type (WT) mice, Aldh2 knockout (KO) mice naturally have a strong bone formation ability, and high expression of parathyroid hormone receptor (PTHR1) in osteocytes. The effect of the Aldh2 gene on bone metabolism in response to intermittent PTH treatment is unknown. The purpose of this study was to clarify the effect of the Aldh2 gene on the bone anabolic response to intermittent PTH treatment in ovariectomized mice. Female KO and WT mice were ovariectomized at 8 weeks of age. At 14 weeks of age, the KO and WT mice were divided into vehicle-treated (Veh) and PTH-treated (PTH) groups (i.e., the WT-Veh, WT-PTH, KO-Veh and KO-PTH groups). PTH (1-34) and vehicle were subcutaneously administered to each group at a dose of 40 µg/kg body weight (BW) five times per week for 4 weeks. Micro-CT showed that the bone volume (BV), trabecular number (Tb.N), connectivity density (Conn.D), and cortical thickness (Ct.Th) values in the KO-PTH mice were significantly higher than those in the KO-Veh mice. Histomorphometric analysis showed that the BV, Tb.N, and mineral apposition rate (MAR) values in the KO-PTH group were significantly higher than those in the KO-Veh group. The mRNA expression level of PTHR1 in the KO-PTH group was significantly increased and that of p21 in the KO-PTH group was significantly decreased compared with the levels in the KO-Veh group. The expression of PTHR in osteocytes from the KO-PTH group was also significantly increased compared with that in osteocytes from the KO-Veh group. Furthermore, cell cultures revealed that the ALP+CFU-f/total CFU-f percentage was significantly higher in the KO-PTH group than in the KO-Veh group. We concluded that in ovariectomized Aldh2 KO mice, the bone anabolic response to intermittent PTH treatment was significantly enhanced compared to that in WT mice, which may be mediated by the high expression level of PTHR1.

Skeletal unloading reduces cluster of differentiation (CD) 38 expression in the bone marrow and osteoblasts of mice.

BACKGROUND: Mechanical unloading induces bone loss in human weight-loaded bones. The findings of recent studies have revealed that cluster of differentiation 38 knockout mice display bone loss similar to that observed in osteoporosis. This study aimed to determine whether the expression of cluster of differentiation 38 is implicated in skeletal unloading and reloading. METHODS: Eight-week-old male C57BL/6J mice were assigned to control, tail-suspension, or reloading after tail-suspension groups. In the tail-suspension group, tail suspension elevated the hind limbs for 1 week. The bilateral femurs and tibias from the groups were evaluated for cluster of differentiation 38 immunocytochemistry, and the cluster of differentiation 38 messenger ribonucleic acid levels and the expression of cluster of differentiation 38 and other cell-surface antigens were evaluated using quantitative real-time polymerase chain reaction and flow cytometric analyses. RESULTS: In the tail-suspension group, the alkaline phosphatase reactivity, cluster of differentiation 38 immunoreactivity in the bone marrow and osteoblasts, and the expression of cluster of differentiation 38 messenger ribonucleic acid and that of other cell-surface antigens were significantly lower than those in the control group. In the reloading after tail-suspension group, the level of cluster of differentiation 38 expression was restored to the same level as that in the control group. CONCLUSIONS: Cluster of differentiation 38 expression declined after skeletal unloading and recovered to normal levels after reloading. In the bone marrow, cluster of differentiation 38 expression plays a crucial role in bone formation in response to mechanical stress.

Current Smoking Is Associated with Delayed Wound Healing But Not with Improvement of Contracture after the Open Palm Technique for Dupuytren's Disease.

BACKGROUND: Some cases treated with open palm technique need relatively long wound healing time. This study aims to clarify whether the preoperative lifestyle-related diseases or factors are associated with surgical results after the open palm technique for Dupuytren's contracture. METHODS: The study included 122 fingers of 84 hands of 84 consecutive male patients with Dupuytren's contracture who were treated with McCash's open palm technique at our hospital from 1980 to 2016. The average age of the patients was 68.0 years (range, 39-86). The follow-up period was at least 6 months (average, 36.3 months). Using multiple regression analysis, we investigated preoperative factors associated with surgical results. The factors examined were age, affected side, contracture of the little finger, number of contracted fingers, contracture of the proximal interphalangeal (PIP) joint, Meyerding classification, diabetes mellitus, hypertension, alcohol intake, and smoking. Surgical results were judged at 6 months after surgery and wound healing time was evaluated. RESULTS: According to Tubiana's criteria, there were 59 excellent hands (70.2%), 18 good hands (21.4%), 5 fair hands (6.0%), and 2 poor hands (2.4%) at the final physical examination after surgery. The average of the percentage of improvement in contracture was 86.1%. The average number of days needed until complete open wound closure was 22.9 days. Multiple regression analysis revealed that the significant preoperative factors associated with the percentage of improvement in contracture were multiple contracted fingers and involvement of PIP joint contracture, and that the factor associated with delayed wound healing was current smoking. CONCLUSIONS: Multiple contracted fingers and involvement of PIP joint contracture are associated with insufficient improvement of joint contracture. Current smoking is associated with delayed wound healing, but not with improvement of joint contracture, after the open palm technique for Dupuytren's disease in men.

Short-term efficacy and safety of collagenase injection for Dupuytren's contracture: Therapy protocol for successful outcomes in a clinical setting.

PURPOSE: To assess the short-term efficacy and safety of collagenase injection for Dupuytren's contracture and of our post-injection therapy protocol alternative the instruction of phase III studies at clinical setting. METHODS: The retrospective study included 23 fingers of 21 hands of 18 patients for primary metacarpophalangeal (MP) joints and 11 fingers of 10 hands of 10 patients for primary proximal interphalangeal (PIP) joints with Dupuytren's contracture who were treated with 0.58 mg collagenase Clostridium histolyticum (CCH) injections at our hospital consecutively from September 2015 to October 2017. The mean age of the patients was 73.0 years (range, 57-88) for primary MP joints and 70.7 years (61-81) for primary PIP joints. Following standard CCH injection and manipulation on the next day, certified hand surgeons evaluated and treated each patient based on a defined 4-week therapy protocol that consisted of performing finger exercises during the day and wearing static extension splint at night for all cases, and of wearing Capener dynamic splint intervention to address severely contracted PIP joints. We measured the degree of contracture at baseline, immediately, 4 weeks, and 12 weeks after the last manipulation. RESULTS: More improvement of contracture was seen in the MP joints than in the PIP joints. For the five fingers severely contracted and treated with Capener splint intervention, the mean passive PIP joint contracture was 62.0° at baseline, 21.0° immediately, further improved to 6.0° by 4 weeks, and maintained 8.0° by 12 weeks after the last manipulation. The adverse events were mild-to-moderate local reactions in the injected hand. CONCLUSIONS: The clinical efficacy and safety of CCH were confirmed in a clinical setting similar to phase III studies. The improvement of 4-week-intervention was maintained at 12 weeks after the last manipulation. Severely contracted PIP joints could benefit from Capener splint intervention.

Effect of estradiol on fibroblasts from postmenopausal idiopathic carpal tunnel syndrome patients.

Fibrosis of the subsynovial connective tissue (SSCT) is a characteristic finding in patients with idiopathic carpal tunnel syndrome (CTS). Idiopathic CTS frequently occurs in postmenopausal women; therefore, female steroid hormones, especially estrogens, may be involved in its development. In this study, we evaluated the effect of the estradiol on the expression of genes and proteins related to fibrosis of SSCT fibroblasts from patients with idiopathic CTS. This study included 10 postmenopausal women (mean age 76 years). Fibroblasts derived from SSCT were treated with estradiol (10-4 -10-12 M), and the expression levels of TGF-ß-responsive genes were evaluated. The relationships between the expression of untreated estrogen receptor α (ERα) and ERß and changes in gene expression due to estradiol treatment were examined by quantitative real-time polymerase chain reaction. The effects of 10-4 M estradiol on collagen type I (Col1) and collagen type III (Col3) protein expression levels were also evaluated by fluorescent staining. The relationships between ERα/ß and Col1/3 expression were evaluated by immunohistochemical staining. The reduction in Col1A1 mRNA expression due to estradiol treatment was positively correlated with ERα expression (r = 0.903, p < 0.01). At the protein level, expression of Col1 and Col3 were down-regulated. These results indicated that ERα-mediated signaling may be involved in the regulation of Col1A1, and its regulatory effect may be dependent on the ERα expression level. The accurate evaluation of ERα expression level in the SSCT of individual patients with idiopathic CTS might guide the effective use of new estrogen replacement therapy.

Disruption of the Aldehyde Dehydrogenase 2 Gene Results in No Increase in Trabecular Bone Mass Due to Skeletal Loading in Association with Impaired Cell Cycle Regulation Through p21 Expression in the Bone Marrow Cells of Mice.

Approximately 45% of people of East Asian descent have the inactive aldehyde dehydrogenase 2 (ALDH2) phenotype. The enzyme defect of ALDH2 has been found to adversely influence the risk of osteoporosis. The aim of this study was to clarify the effect of skeletal loading on trabecular bone structure and dynamics in Aldh2-disrupted mice in the absence of alcohol consumption. Four-week-old male Aldh2-/- (KO) and Aldh2+/+ (WT) mice were divided into a ground control (GC) group and a climbing exercise (CE) group in each genotype. The trabecular bone mineral density of the distal femur measured by peripheral quantitative computed tomography in the wild-type CE (WTCE) group was significantly higher than that in the wild-type GC (WTGC) group; however, there was no significant difference between the knockout CE (KOCE) and knockout GC (KOGC) groups. Bone histomorphometry revealed that osteogenic parameters were significantly increased in the WTCE group compared with the WTGC group, but not increased in the KOCE group compared with the KOGC group. Quantitative reverse transcriptase polymerase chain reaction and flow cytometry revealed that mRNA and protein expression levels of p21 were significantly decreased in the WTCE group compared with those in the WTGC group, while these differences were not observed between the KOGC and KOCE groups. This study provides the first in vivo evidence that p21 expression in the bone marrow is not decreased after skeletal loading and osteoblast differentiation is impaired in the absence of Aldh2 gene.

Elcatonin prevents bone loss caused by skeletal unloading by inhibiting preosteoclast fusion through the unloading-induced high expression of calcitonin receptors in bone marrow cells.

This study aimed to clarify whether elcatonin (EL) has a preventive action on bone dynamics in skeletal unloading. Seven-week-old male C57BL/6J mice with either ground control (GC) or tail suspension (TS) were administered EL 20U/kg or a vehicle (veh) three times per week and assigned to one of the following four groups: GCEL, GCveh, TSEL, and TSveh. Blood samples and bilateral femurs and tibias of the mice were obtained for analysis. After 7days of unloading, the trabecular bone mineral density in the distal femur obtained via peripheral quantitative computed tomography and the trabecular bone volume were significantly higher in the TSEL group than in the TSveh group. The bone resorption histomorphometric parameters, such as the osteoclast surface and osteoclast number, were significantly suppressed in the TSEL mice, whereas the number of preosteoclasts was significantly increased. The plasma level of tartrate-resistant acid phosphatase-5b (TRACP-5b) was significantly lower in the TSEL group than in all other groups. In the bone marrow cell culture, the number of TRACP-positive (TRACP(+)) multinucleated cells was significantly lower in the TSEL mice than in the TSveh mice, whereas the number of TRACP(+) mononucleated cells was higher in the TSEL mice. On day 4, the expression of nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1), cathepsin K and d2 isoform of vacuolar ATPase V0 domain (ATP6V0D2) mRNA in the bone marrow cells in the TSEL mice was suppressed, and the expression of calcitonin receptor (Calcr) mRNA on day 1 and Calcr antigen on day 4 were significantly higher in the TSveh mice than in the GCveh mice. EL prevented the unloading-induced bone loss associated with the high expression of Calcr in the bone marrow cells of mouse hindlimbs after tail suspension, and it suppressed osteoclast development from preosteoclasts to mature osteoclasts through bone-resorbing activity. This study of EL-treated unloaded mice provides the first in vivo evidence of a physiological role of EL in the inhibition of the differentiation process from preosteoclasts to osteoclasts.

[Pharmacology of bone resorption inhibitor].

Currently, bone resorption inhibitor is mainly used for osteoporosis. A number of these agents have been developed. These pharmacological action are various. Bisphosphonate inhibit functions of the osteoclasts by inducing apoptosis. On the one hand, RANK-ligand inhibitor and selective estrogen receptor modulator inhibit formation of osteoclasts. It is important to understand these pharmacological action for the selection of the appropriate medicine.

Negative Pressure Wound Therapy with Surgical Gloves to Repair Soft Tissue Defects in Hands.

The efficacy of negative pressure wound therapy (NPWT) in the treatment of skin defect wounds has been established, but it is difficult to apply to hand surgery because of the easy occurrence of air leaks. We report two cases of performing NPWT with surgical gloves. Case1: A 37-year-old male was injured on his right dorsal hand from a punch. He presented to our hospital three days after the injury because of swelling and pain. The wound was infected and contused, so wound lavage and debridement (W&D) were performed under local anesthesia. The infected condition didn't improve after antimicrobial infusion, so W&D were performed again 8 days after the first visit. Then W&D were performed every day, and the infection subsided 15 days after the first visit. NPWT was initiated for the purpose of managing exudate and the wound condition, and healthy granulation tissue formed gradually. Finally, transpositional flap and full-thickness skin graft were performed on day 29. Case2: A 43-year-old male accidentally sustained a high pressure injection of oil into his dorsal hand. He presented to our hospital the next day, and W&D were performed. W&D were performed again two days after the first visit, and artificial dermis was applied over a part of the wound that was impossible to close. A decision was made to apply NPWT and a surgical glove for the purpose of reducing swelling and managing wound exudate. The swelling decreased and granulation tissue formed gradually, then nine days after the first visit a sural nerve graft was applied to bridge the defective area, and a full thickness skin graft was applied. We achieved good wound closure and hand function recovery after using NPWT and a surgical glove.

Enhanced expression of Wnt9a in the flexor tenosynovium in idiopathic carpal tunnel syndrome.

This study aimed to clarify the association between abnormal Wnt signaling and the cause of idiopathic carpal tunnel syndrome (ICTS) and whether an association exists between Wnt signaling and cell proliferation in the flexor tenosynovium. The subjects included nine patients with ICTS; the controls were nine patients with distal radius fractures without any symptoms of carpal tunnel syndrome. We extracted mRNA from the flexor tenosynovium and compared the expression levels of genes encoding 17 types of Wnt in both subjects and controls via quantitative real-time polymerase chain reaction (PCR). Expression levels of factors involved in cell proliferation, such as estrogen-responsive finger protein, epidermal growth factor receptor, heparin binding-epidermal growth factor-like growth factor, insulin-like growth factor-1, and vascular endothelial growth factor (VEGF) were also measured using quantitative real-time PCR. In addition, we compared the Wnt and MIB-1 protein expression levels to clarify the effect of Wnt on cell proliferation. Quantitative real-time PCR revealed significantly greater expression of the gene encoding Wnt9a in subjects with ICTS than in controls and also revealed a positive correlation between the expression of genes encoding Wnt9a and VEGF in subjects with ICTS. Quantitative evaluation using immunohistochemical staining also indicated more marked Wnt9a expression in subjects than in controls. However, there was no relationship between the expression of Wnt9a and the cell proliferation index MIB-1. These results indicate that Wnt9a expression is enhanced in ICTS and that Wnt9a may be involved in VEGF expression in ICTS.

Post-traumatic malunion of the distal radial intra-articular fractures treated with autologous costal osteochondral grafts and bioabsorbable plates.

Intra-articular distal radial fractures with partial bone loss at the wrist were reconstructed using osteochondral grafts in 2 patients who were followed up for at least 18 months. Both patients experienced posttraumatic arthrosis of the wrist joint. The materials of the intra-articular fixation were bioabsorbable plates and screws. Reconstruction of a partially destroyed articular surface using a costal osteochondral graft is reliable and allows filling and resurfacing an articular cartilage void.

Extensor pollicis longus tendon ruptures after the use of volar locking plates for distal radius fractures.

Currently, volar locking plates are commonly used to treat distal radius fractures (DRF) because of their stable biomechanical construct and because they cause less soft tissue disturbance and allow early mobilisation of the wrist. Complications such as rupture of tendons have been reported to occur with use of volar locking plates. We describe six cases of rupture of extensor pollicis longus (EPL) tendons after the use of volar locking plates. EPL tendon injuries occurred in 2.1% (6/286) of cases after DRF surgery. The causes of EPL rupture after DRF surgery were protrusion of the head tip and insufficient reduction of the dorsal roof fragment of the distal radius. These were considered iatrogenic problems. The cause of EPL rupture was unknown in three cases. We should be extremely careful when determining optimum screw length and reducing displaced dorsal roof fragments to prevent damaging the EPL tendons.

Mechanical comparison of novel bioabsorbable plates with titanium plates and small-series clinical comparisons for metacarpal fractures.

BACKGROUND: The use of bioabsorbable implants to negate the need for subsequent removal could offer major clinical advantages for the fixation of fractures. The aims of this study were to compare the mechanical properties of novel bioabsorbable plates with those of titanium plates in a fracture model and to demonstrate the clinical results of the use of these new plates for metacarpal fractures. METHODS: The first set of experiments compared the mechanical properties of bioabsorbable and titanium plates. Two types of bioabsorbable plates (one-third tubular and semi-tubular in cross-section) made of hydroxyapatite/poly-L-lactide and two types of titanium plates (for 1.5 and 2.0-mm screws) were tested. Each plate was fixed on a polyether ether ketone (PEEK) rod, which was transversely cut at its midsection. The second part of the study compared the clinical results associated with the bioabsorbable and titanium plates that were used in sixteen nonrandomized consecutive patients with metacarpal fractures. RESULTS: The bending strength and stiffness of one-third tubular bioabsorbable plate constructs were comparable with those of titanium plates for 1.5-mm screws, and those of one-half tubular bioabsorbable plates were comparable with those of titanium plates for 2.0-mm screws. The mean torsional strength (and standard deviation) of the semi-tubular bioabsorbable plates (79.0 ± 7.9 N.cm) was significantly greater than that of titanium plates for 2.0 mm screws (56.7 ± 4.0 N.cm) (p < 0.05). There were no significant differences in six-month postoperative clinical results between patients who received bioabsorbable plates and those who received titanium plates (total range of active motion, 267.0° ± 6.0° compared with 250.0° ± 28.3°; grip strength, 92.7% ± 19.7% compared with 86.4% ± 28.6% of that on the contralateral side). CONCLUSIONS: The bending strength, stiffness, and torsional strength of novel one-third or semi-tubular bioabsorbable plates, when fixed on a PEEK rod, were comparable with those for titanium plates for 1.5 or 2.0-mm screws. There were no significant differences in clinical results between these two types of plates in a small group of patients after short-term follow-up.

Linburg-Comstock syndrome: a case report.

We report a case of Linburg-Comstock syndrome, which is characterized with anomalous tendon slips connecting flexor pollicis longus (FPL) to the flexor digitorum profundus (FDP), usually at the index finger. The present patient started to be a carpenter and was suffering from his disability of flexing the thumb and the index finger independently when he handled the screws in his work. We surgically removed the tendinous connection of the FPL tendon and the index FDP tendon. After surgery, he could work as a carpenter without any difficulty. Surgical disconnection was effective treatment. Dynamic high-resolution ultrasound and three dimensions of computed tomography of the left distal forearm were helpful to confirm the diagnosis.

Reduced bone formation in alcohol-induced osteopenia is associated with elevated p21 expression in bone marrow cells in aldehyde dehydrogenase 2-disrupted mice.

INTRODUCTION: High consumption of alcohol is one of the risk factors for osteoporosis. Approximately 45% of Chinese and Japanese individuals have the inactive aldehyde dehydrogenase 2 (Aldh2) phenotype. The absence of the ALDH2*2 allele is found to adversely influence the risk of osteoporosis. The aim of this study is to clarify the effects of alcohol consumption on osteoblast differentiation in bone marrow and trabecular bone formation in Aldh2-disrupted mice. MATERIALS AND METHODS: Seven-week-old male Aldh2 knockout mice (Aldh2(-/-)) and wild-type (Aldh2(+/+)) mice were fed with water (groups Aldh2(-/-)/Wa and Aldh2(+/+)/Wa) or with 5% ethanol (groups Aldh2(-/-)/Al and Aldh2(+/+)/Al) for 4 weeks. At the age of 12 weeks, bone histomorphometry was performed at the secondary spongiosa of the tibias. Bone marrow cells from the bilateral femurs and tibias were used for mRNA expression analysis. RESULTS: Histomorphometrical study revealed that trabecular bone was significantly reduced in the Aldh2(-/-)/Al group compared with that in the Aldh2(-/-)/Wa and Aldh2(+/+)/Wa groups. Bone formation rate was significantly decreased in Aldh2(-/-)/Al compared with the other three groups. Quantitative RT-PCR revealed a significant decrease in type I collagen, osterix, osteopontin, and osteocalcin mRNA expressions in Aldh2(-/-)/Al compared with Aldh2(-/-)/Wa. In bone marrow cell cultures, mineralized nodule formation in Aldh2(-/-)/Al was significantly decreased compared with that in Aldh2(+/+)/Wa and Aldh2(-/-)/Wa, while PAK18, a p21-activated kinase inhibitor, recovered the decreased mineralized nodule formation in Aldh2(-/-)/Al. CONCLUSION: Alcohol consumption suppressed the differentiation and mineralization of osteoblasts and then reduced trabecular bone formation and bone volume in association with the elevated p21 expression in bone marrow cells, especially in aldehyde dehydrogenase 2-disrupted mice.

Climbing exercise enhances osteoblast differentiation and inhibits adipogenic differentiation with high expression of PTH/PTHrP receptor in bone marrow cells.

We developed previously a mouse voluntary climbing exercise model as a physiological mechanical loading model and reported that climbing exercise increased bone formation, but its effect on adipogenesis is unknown. We assessed the effects of loading and PTH/PTHrP receptor (PTHR1) on bone marrow adipocyte differentiation in relation with osteoblast differentiation. 8-week-old C57BL/6J male mice were divided into ground control (GC) and climbing exercise (EX) group. Mice were housed in 100-cm towers and climbed up toward a bottle placed at the top of the cage to drink water. The values of bone volume and osteoblast number were significantly higher while those of marrow adipocyte volume and number were significantly lower in the 28dayEX group than 28dayGC group. The mRNA expression levels of adipocyte differentiation genes CCAAT/enhancer-binding proteins (C/EBP) beta and delta were lower in 4dayEX mice, while the adipocyte specific genes fatty acid binding protein (aP2) and phosphoenolpyruvate carboxykinase (PEPCK) expressions were lower in 7dayEX mice. In primary bone marrow cell cultures, the number of alkaline phosphatase-positive colony forming units-fibroblastic (ALP+ CFU-f) and Oil-red-O-positive cells were both increased in the 4dayEX group. Climbing exercise transiently increases both osteogenic and adipogenic potential in bone marrow stromal cells, and inhibits terminal adipocyte differentiation and promotes osteoblast differentiation. Immunoreactivity for the PTHR1 was intense on osteoblastic cell lineage in the endosteal tibial metaphysis. PTHR1 mRNA expression was increased in 4dayEX mice and PTHR1-positive cells were increased after 7 days in the experimental group. Ex vivo addition of PTHR1 antibody decreased and that of PTHrP(1-34) increased the number of ALP+ CFU-f in bone marrow cell cultures obtained at 4 days after the exercise, while the addition of PTHR1 antibody increased and PTHrP(1-34) decreased the number of Oil-red-O-positive cells. Our results indicate that climbing exercise enhanced osteoblast differentiation and inhibited terminal differentiation of adipocyte progenitors with high expression of PTHR1 in bone marrow cells.

Selective cyclooxygenase-2 inhibitor prevents reduction of trabecular bone mass in collagen-induced arthritic mice in association with suppression of RANKL/OPG ratio and IL-6 mRNA expression in synovial tissues but not in bone marrow cells.

We performed this study to clarify whether celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, prevents trabecular bone mass reduction by suppressing arthritis-related increase of bone resorption, and to discriminate differences in actions on bone among celecoxib, SC-58560 (a selective COX-1 inhibitor), and indomethacin. Eight-week-old DBA/1J male mice were divided into six groups as follows. Control untreated (Normal) and collagen-induced arthritic (CIA) mice were compared with four treatment groups: celecoxib was orally administered to CIA mice at doses of 0 (Vehicle), 16 (COX2L), and 75 (COX2H) mg/kg, in addition to two groups of mice treated with SC-58560 (COX1) or indomethacin (IND). Histomorphometry showed a significant decrease in tibial trabecular bone volume in arthritic mice, which was corrected by COX2H. The increased osteoclast surface and number in the Vehicle group were suppressed by COX2L, COX2H, and IND. The decreased bone formation rate in Vehicle was elevated by COX2H without statistical significance. A high ratio of mRNA expression of receptor activator of NF-kappaB ligand (RANKL)/osteoprotegerin (OPG) in Vehicle synovial tissue was suppressed by COX2L and COX2H. The increased expression of interleukin (IL)-6 mRNA in Vehicle was suppressed by COX2L, COX2H, and IND, although no difference in this expression was observed in bone marrow cells among all groups. In conclusion, in CIA mice, celecoxib suppresses arthritis-related increase in bone resorption at low and high doses and prevents trabecular bone mass reduction at high doses in association with suppression of osteoclast development in bone marrow through inhibition of RANKL/OPG ratio and IL-6 mRNA expression in inflammatory synovial tissue.