Osteoporosis and Osteopenia in patients with psoriatic arthritis: a single-center retrospective study.

OBJECTIVE: It is known that fracture risk is increased in patients with psoriatic arthritis (PsA), however, there is no consensus on the association with osteoporosis. The purpose of this study was to elicit the rate of osteoporosis and the risk factors of osteoporosis in patients with PsA at our institution. METHODS: The data in this study were extracted from 163 patients with PsA. Osteoporosis and osteopenia were defined based on the WHO definition. Osteoporosis was also diagnosed when a fragility vertebral compression fracture was observed. RESULTS: The osteoporosis and osteopenia rates for PsA patients were 11.7% and 33.1%, respectively. The rates of osteoporosis and osteopenia in males were particularly high compared to previous reports, at 9.3% and 34.3%, respectively. Trabecular bone score (TBS) was considered age-appropriate for both males and females. Body mass index (BMI) and TBS were significantly lower in patients with osteoporosis. CONCLUSIONS: In patients with PsA, males are at elevated risk of osteoporosis and associated fragility fractures even if they are under 50 years old. BMI was significantly lower in osteoporotic cases, suggesting the importance of bone mineral density testing and treatment in such cases.

Iguratimod suppresses sclerostin and receptor activator of NF-κB ligand production via the extracellular signal-regulated kinase/early growth response protein 1/tumor necrosis factor alpha pathway in osteocytes and ameliorates disuse osteoporosis in mice.

Disuse osteoporosis is a prevalent complication among patients afflicted with rheumatoid arthritis (RA). Although reports have shown that the antirheumatic drug iguratimod (IGU) ameliorates osteoporosis in RA patients, details regarding its effects on osteocytes remain unclear. The current study examined the effects of IGU on osteocytes using a mouse model of disuse-induced osteoporosis, the pathology of which crucially involves osteocytes. A reduction in distal femur bone mass was achieved after 3 weeks of hindlimb unloading in mice, which was subsequently reversed by intraperitoneal IGU treatment (30 mg/kg; five times per week). Histology revealed that hindlimb-unloaded (HLU) mice had significantly increased osteoclast number and sclerostin-positive osteocyte rates, which were suppressed by IGU treatment. Moreover, HLU mice exhibited a significant decrease in osteocalcin-positive cells, which was attenuated by IGU treatment. In vitro, IGU suppressed the gene expression of receptor activator of NF-κB ligand (RANKL) and sclerostin in MLO-Y4 and Saos-2 cells, which inhibited osteoclast differentiation of mouse bone marrow cells in cocultures. Although IGU did not affect the nuclear translocation or transcriptional activity of NF-κB, RNA sequencing revealed that IGU downregulated the expression of early growth response protein 1 (EGR1) in osteocytes. HLU mice showed significantly increased EGR1- and tumor necrosis factor alpha (TNFα)-positive osteocyte rates, which were decreased by IGU treatment. EGR1 overexpression enhanced the gene expression of TNFα, RANKL, and sclerostin in osteocytes, which was suppressed by IGU. Contrarily, small interfering RNA-mediated suppression of EGR1 downregulated RANKL and sclerostin gene expression. These findings indicate that IGU inhibits the expression of EGR1, which may downregulate TNFα and consequently RANKL and sclerostin in osteocytes. These mechanisms suggest that IGU could potentially be used as a treatment option for disuse osteoporosis by targeting osteocytes.

Paediatric pustulotic arthro-osteitis patient with an IL36RN variant, heterozygous c.115+6T>C, who was successfully treated with tonsillectomy: A case report and literature review.

Pustulotic arthro-osteitis (PAO) is an infrequent condition, with its manifestation in children being even rare. Some reports propose an association between genetic variants and the onset of PAO. Currently, no definitive treatment protocol exists for paediatric patients with PAO. In this study, we present the paediatric case of PAO with an IL36RN variant who was successfully treated with tonsillectomy.

Early full weight-bearing and gait exercise after cemented total ankle arthroplasty with modified antero-lateral approach.

BACKGROUND: According to the conventional postoperative procedure after total ankle arthroplasty (TAA) against end-stage osteoarthritis (OA) and rheumatoid arthritis (RA), mobilization and weight-bearing is currently started after completion of wound healing. Recently, early mobilization for dorsiflexion after TAA with modified antero-lateral approach was reported to be feasible and safe. To investigate the further possibility of expediting rehabilitation, this study evaluated the feasibility and safety of early full weight-bearing and gait exercise after cemented TAA utilizing a modified antero-lateral approach. MATERIALS AND METHODS: This retrospective, observational study investigated 23 consecutive ankles (OA: 14 ankles, RA: 9 ankles) that had received cemented TAA with a modified antero-lateral approach. These ankles were divided into three groups [1. conventional postoperative protocol: 8 ankles, 2. early dorsiflexion protocol: 7 ankles, 3. early dorsiflexion+full weight-bearing protocol: 8 ankles]. In group 3, after early dorsiflexion mobilization (day 3), full weight-bearing/gait exercise was started from 7 days after surgery (10 days after if malleolar osteotomy was added). Postoperative wound complications were observed and recorded. Number of days for hospitalization was also evaluated. Range of motion (ROM) of dorsiflexion/plantar flexion was measured. Patients also completed a self-administered foot evaluation questionnaire (SAFE-Q) and the scale of Japanese Society for Surgery of the Foot (JSSF) ankle/hindfoot score preoperatively and at final follow-up. RESULTS: No postoperative complications related to wound healing were observed even after early full weight-bearing and gait exercise. Days for hospitalization was significantly shortened in early full weight-bearing and gait exercise group (group 3) from 35-38 days to 24 days. ROM for both dorsiflexion and plantar flexion significantly increased in group 3, furthermore all indices of SAFE-Q score also showed stronger significant improvement in group 3. JSSF score improved significantly after TAA in all groups. CONCLUSION: Within this small number of cases, early full weight-bearing and gait exercise from 7 days after cemented TAA was feasible and safe with the modified antero-lateral approach. Combination of early dorsiflexion mobilization and weight-bearing/gait exercise contributed to shortening the hospitalization day, and improving ROM for both dorsiflexion and plantar flexion after surgery. Innovations in postoperative procedures for rehabilitation after TAA can be expected.

Real-world retention rates of biologics in patients with rheumatoid arthritis.

Although biologics have their own characteristics, there are no clear criteria for selecting them to treat the patients with rheumatoid arthritis. To assist in selecting biologics, we investigated the retention rates of biologics at our institution. We examined retention rates, and reasons for dropout for biologics in 393 cases and 605 prescriptions (of which 378 prescriptions were as naive) at our hospital since October 2003. Throughout the entire course of the study, etanercept (ETN) was the most frequently used biologic, followed by adalimumab (ADA) and tocilizumab (TCZ). When narrowed down to the later period from 2010, ETN was still the most used, followed by TCZ and abatacept (ABT). When the retention rates were compared in biologic naive patients, the retention rates were TCZ, ABT, ETN, certolizumab pegol (CZP), golimumab (GLM), infliximab (IFX), and ADA, in that order. The retention rates were better with the first use of each biologic. The main reasons for dropout were primary ineffectiveness, secondary ineffectiveness, and infection. ETN was the most used biologic in our hospital, with an increasing trend toward the use of non-TNF inhibitors. Retention rates were higher in non-TNF inhibitors.

Long-term retention rates of anti-tumour necrosis factor and anti-interleukin-17 antibodies for patients with psoriatic arthritis.

OBJECTIVE: While biologics have been used for the patients with psoriatic arthritis, there remains to be unknown concerning long-term retention rates. This study aims to present real-world data about long-term retention rates of biologics for the patients with psoriatic arthritis, and to undertake an analysis of the contributing factors. METHODS: We examined retention rates and the reasons for discontinuation for biologics (adalimumab, certolizumab pegol, secukinumab, and ixekizumab) in 146 prescriptions (of which, 109 prescriptions were as naive) at our hospital since March 2010. RESULTS: Throughout the entire course of the study, the 10-year retention rates were approximately 70% for adalimumab, 50% for ixekizumab, and 40% for secukinumab. When evaluating retention rates in the biologic-naïve subgroups, the 10-year retention rates were all approximately 70%. Regarding certolizumab pegol, the 3-year retention rate was approximately 75%. For adalimumab, a higher degree of arthritis at the initiation of treatment was found to correlate with an increased likelihood of secondary inefficacy. The main reason for discontinuation was secondary inefficacy, except for ixekizumab. CONCLUSIONS: Each biologic exhibited a favourable long-term retention rate. The main reason for discontinuation was secondary inefficacy. Regarding adalimumab, secondary inefficacy was linked to the extent of arthritis upon treatment initiation.

Anti-NF-κB peptide derived from nuclear acidic protein attenuates ovariectomy-induced osteoporosis in mice.

NF-κB is a transcription factor that is activated with aging. It plays a key role in the development of osteoporosis by promoting osteoclast differentiation and inhibiting osteoblast differentiation. In this study, we developed a small anti-NF-κB peptide called 6A-8R from a nuclear acidic protein (also known as macromolecular translocation inhibitor II, Zn2+-binding protein, or parathymosin) that inhibits transcriptional activity of NF-κB without altering its nuclear translocation and binding to DNA. Intraperitoneal injection of 6A-8R attenuated ovariectomy-induced osteoporosis in mice by inhibiting osteoclast differentiation, promoting osteoblast differentiation, and inhibiting sclerostin production by osteocytes in vivo with no apparent side effects. Conversely, in vitro, 6A-8R inhibited osteoclast differentiation by inhibiting NF-κB transcriptional activity, promoted osteoblast differentiation by promoting Smad1 phosphorylation, and inhibited sclerostin expression in osteocytes by inhibiting myocyte enhancer factors 2C and 2D. These findings suggest that 6A-8R has the potential to be an antiosteoporotic therapeutic agent with uncoupling properties.

Preoperative degree of deformity and underlying disease affect the postoperative deformity of joint-preserving hallux valgus surgery.

BACKGROUND: The combination of distal osteotomy with lateral dissection in joint-preserving surgery for severe hallux valgus deformity has recently begun to yield encouraging results. We examined the frequency of complications and risk factors of those for joint-preserving surgery in patients with and without rheumatoid arthritis (RA). METHODS: A retrospective, observational study of 72 feet (27 patients with RA) was performed. The inclusion criteria were patients who underwent joint-preserving surgery for hallux valgus deformity at our hospital between January 2008 and March 2016 who could be followed up with for longer than 12 months. RESULTS: The mean preoperative and immediate postoperative hallux valgus angles (HVA) were 41.8 and 4.4, respectively. The mean preoperative and immediate postoperative intermetatarsal angles between the first and second metatarsal bones (M1-M2A) were 14.6 and 5.8, respectively. At the final postoperative evaluation, the mean HVA was 8.8 and the mean M1-M2A was 6.4.Data were compared among the patients with complications (recurrent valgus deformity, varus deformity), and those without complications (normal HVA) at the final postoperative evaluation. The rate of RA in the varus deformity group was 71.4%, which tended to be higher than in other groups (p = .058). The mean preoperative HVA were 48.2 and 52.6 in the group of recurrent valgus deformity and varus deformity, which was higher than the normal HVA group (p = .001). CONCLUSIONS: High preoperative HVA was a risk factor for the recurrence of valgus deformity. Most of the varus deformities were observed in the RA group with high preoperative HVA; therefore, caution should be exercised in operating on patients with severe deformity or those with RA. LEVEL OF EVIDENCE: III.

Basic fibroblast growth factor promotes meniscus regeneration through the cultivation of synovial mesenchymal stem cells via the CXCL6-CXCR2 pathway.

OBJECTIVE: To investigate the efficacy of basic fibroblast growth factor (bFGF) in promoting meniscus regeneration by cultivating synovial mesenchymal stem cells (SMSCs) and to validate the underlying mechanisms. METHODS: Human SMSCs were collected from patients with osteoarthritis. Eight-week-old nude rats underwent hemi-meniscectomy, and SMSCs in pellet form, either with or without bFGF (1.0 × 106 cells per pellet), were implanted at the site of meniscus defects. Rats were divided into the control (no transplantation), FGF (-) (pellet without bFGF), and FGF (+) (pellet with bFGF) groups. Different examinations, including assessment of the regenerated meniscus area, histological scoring of the regenerated meniscus and cartilage, meniscus indentation test, and immunohistochemistry analysis, were performed at 4 and 8 weeks after surgery. RESULTS: Transplanted SMSCs adhered to the regenerative meniscus. Compared with the control group, the FGF (+) group had larger regenerated meniscus areas, superior histological scores of the meniscus and cartilage, and better meniscus mechanical properties. RNA sequencing of SMSCs revealed that the gene expression of chemokines that bind to CXCR2 was upregulated by bFGF. Furthermore, conditioned medium derived from SMSCs cultivated with bFGF exhibited enhanced cell migration, proliferation, and chondrogenic differentiation, which were specifically inhibited by CXCR2 or CXCL6 inhibitors. CONCLUSION: SMSCs cultured with bFGF promoted the expression of CXCL6. This mechanism may enhance cell migration, proliferation, and chondrogenic differentiation, thereby resulting in superior meniscus regeneration and cartilage preservation.

Extensive subcutaneous emphysema of the thigh as a rare complication following total knee arthroplasty: A case report.

INTRODUCTION AND IMPORTANCE OF THE CASE: This is the first report of subcutaneous emphysema of the thigh as a complication after total knee arthroplasty (TKA). PRESENTATION OF CASE: A 78-year-old female patient with valgus knee arthropathy underwent TKA. Two days postoperatively, the patient experienced left thigh swelling and pain, and subcutaneous emphysema was detected upon palpation. Although the skin tone was comparable to the other side, the left thigh was tender and firm. The surgical wound did not exhibit erythema. Computed tomography imaging revealed emphysema in the subcutaneous and intermuscular regions of the left thigh. Gram stain and culture tests from arthrocentesis were negative, and blood culture results were also negative. As there was no fever or disturbance of consciousness, and the LRINEC score was 1, supportive care was provided to the patient. At 5 days postoperatively, there was an observable improvement in the emphysema, and by day 9 postoperatively, the emphysema had fully resolved. CLINICAL DISCUSSION: There is a lack of documented cases reporting extensive subcutaneous emphysema of the thigh following TKA, suggesting it to be an exceedingly rare complication. In this case, we conducted a thorough investigation to assess the potential association of infection. Subsequently, the symptoms were successfully alleviated with supportive care without antibiotics. CONCLUSION: The occurrence of subcutaneous emphysema in the thigh was identified as a postoperative complication following TKA. Blood tests, culture tests and LRINEC score can be valuable tools for differentiation.

Association of the Clinical and Radiographic Findings at Onset With Future Joint Destruction in Patients With Rheumatoid Arthritis.

OBJECTIVES: Since inflammation can cause joint destruction in patients with rheumatoid arthritis (RA), it is assumed that joints that are symptomatic at onset are at higher risk of joint destruction; however, this theory remains controversial. This study aimed to investigate whether the progression of joint destruction in hands and feet could be predicted from the clinical and radiographic findings at onset. METHODS: This study included 75 patients who visited our hospital within one year after the onset of RA with at least 12 months of follow-up. We examined the positive predictive value (PPV) and the sensitivity of the clinical findings (swelling, tenderness, and squeeze test) and joint destruction at onset for the progression of joint destruction. RESULTS: Sixty joints (45 metacarpophalangeal and proximal interphalangeal joints, 15 metatarsophalangeal joints) exhibited progressive structural destruction during the study course. Both the PPV and the sensitivity of the clinical findings for the progression of joint destruction were low; however, only the sensitivity of the squeeze test for the feet was high. The PPV of joint destruction at onset was higher than the clinical findings, and the sensitivity of joint destruction at onset was as high as the squeeze test for the feet.  Conclusions: Regular follow-up with imaging is necessary regardless of symptoms and joint destruction at the onset. Adding the squeeze test for feet to routine clinical practice may help predict the risk of joint destruction for the feet.

Early mobilization of dorsiflexion from 3 days after cemented total ankle arthroplasty with modified antero-lateral approach.

BACKGROUND: According to the conventional postoperative procedure after total ankle arthroplasty (TAA), mobilization is currently started after completion of wound healing. To investigate the possibility of expediting rehabilitation, this study evaluated the feasibility and safety of early mobilization of dorsiflexion after cemented TAA utilizing a modified antero-lateral approach. MATERIALS AND METHODS: This retrospective, observational study investigated 14 consecutive ankles that had received cemented TAA. Mobilization of dorsiflexion was started from 3 days after surgery. Postoperative wound complications including blister formation, eschar formation, wound dehiscence, peri-incisional decreased sensation were observed and recorded. Range of motion (ROM) of dorsiflexion/plantar flexion was measured. Patients also completed a self-administered foot evaluation questionnaire (SAFE-Q) and the scale of Japanese Society for Surgery of the Foot (JSSF) ankle/hindfoot score preoperatively and at final follow-up. RESULTS: No postoperative complications related to wound healing were observed. ROM for dorsiflexion, SAFE-Q score, and JSSF score improved significantly after TAA. CONCLUSION: Within this small number of cases, early mobilization of dorsiflexion from 3 days after cemented TAA was feasible and safe with the modified antero-lateral approach. Innovations in postoperative procedures for rehabilitation after TAA can be expected.

Modified Scarf Osteotomy with Medial Capsular Interposition Combined with Metatarsal Shortening Offset Osteotomy: A Comparison of Patients with Noninflammatory Arthritis and Rheumatoid Arthritis of the Foot.

BACKGROUND: Patients who have noninflammatory arthritis of the feet may develop destructive changes on the first metatarsal head and painful dislocation of the metatarsophalangeal (MTP) joint of 1 or more lesser toes. This aim of this study was to compare feet with noninflammatory arthritis and those with rheumatoid arthritis (RA) with respect to the clinical and radiographic outcomes after treatment of these destructive deformities with a modified Scarf osteotomy with medial capsular interposition into the newly formed first MTP joint, combined with metatarsal shortening offset osteotomy. METHODS: A retrospective observational study of 93 feet (31 with noninflammatory arthritis and 62 with RA) was performed. Hallux and lesser-toe scores on the Japanese Society for Surgery of the Foot (JSSF) scoring system, a self-administered foot evaluation questionnaire (SAFE-Q), and preoperative and postoperative radiographic parameters were evaluated. RESULTS: There were significant improvements at the time of the final follow-up in the mean scores on the hallux and lesser-toe scales of the JSSF system and in the SAFE-Q score. The postoperative JSSF lesser-toes function score was better for the feet with noninflammatory arthritis feet than the feet with RA. There was no significant difference in the hallux valgus angle (HVA) between 1 month postoperatively and the final follow-up for both groups. Furthermore, the HVA showed a strong correlation between the 1-month and final follow-up values. CONCLUSIONS: The combination of the modified Scarf osteotomy with medial capsular interposition and shortening metatarsal offset osteotomy was useful and safe in feet with noninflammatory arthritis. The HVA at 1 month after surgery is useful to predict the HVA within 5 years after surgery. The postoperative clinical score for the lesser toes was better in the feet with noninflammatory arthritis. LEVEL OF EVIDENCE: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

Effects of prior osteoporosis treatment on 12-month treatment response of romosozumab in patients with postmenopausal osteoporosis.

OBJECTIVES: To investigate the effects of prior treatment and determine the predictors of a 12-month treatment response of romosozumab (ROMO) in 148 patients with postmenopausal osteoporosis. METHODS: In this prospective, observational, and multicenter study, treatment naïve patients (Naïve; n=50) or patients previously treated with bisphosphonates (BP; n=37) or denosumab (DMAb; n=45) or teriparatide (TPTD; n=16) (mean age, 75.0 years; T-scores of the lumbar spine [LS] -3.2 and total hip [TH] -2.6) were switched to ROMO due to insufficient effects of prior treatment. Bone mineral density (BMD) and serum bone turnover markers were evaluated for 12 months. RESULTS: At 12 months, changes in LS BMD were Naïve (18.2%), BP (10.2%), DMAb (6.4%), and TPTD (11.2%) (P<0.001 between groups) and changes in TH BMD were Naïve (5.6%), BP (3.3%), DMAb (0.6%), and TPTD (4.4%) (P<0.01 between groups), respectively. In all groups, the LS BMD significantly increased from baseline at 6 and 12 months, although only the DMAb group failed to obtain a significant increase in TH BMD during 12-month treatment. Mean values of N-terminal type I procollagen propeptide (PINP; µg/L) from baseline → 1 month → 12 months were Naïve (67.9 → 134.1 → 51.0), BP (32. 2 → 81.7 → 40.9), DMAb (30.4 → 56.2 → 75.3), and TPTD (97.4 → 105.1 → 37.1), and those of isoform 5b of tartrate-resistant acid phosphatase (TRACP-5b; mU/dL) were Naïve (500.4 → 283.8 → 267.1), BP (273.4 → 203.1 → 242.0), DMAb (220.3 → 246.1 → 304.8), and TPTD (446.6 → 305.1 → 235.7), respectively. Multiple regression analysis revealed that the significant predictors of BMD change at 12 months were difference of prior treatment (r=-2.8, P<0.001) and value of PINP at 1 month (r=0.04, P<0.01) for LS, and difference of prior treatment (r=-1.3, P<0.05) and percentage change of TRACP-5b at 1 month (r=-0.06, P<0.05) for TH. CONCLUSIONS: The early effects of ROMO on LS and TH BMD increase at 12 months were significantly affected by the difference of prior treatment and are predicted by the early change in bone turnover markers.

Effects of iguratimod on glucocorticoid-induced disorder of bone metabolism in vitro.

INTRODUCTION: Glucocorticoids are widely used to treat various diseases including rheumatoid arthritis (RA); however, one of the most frequent and severe adverse effects is glucocorticoid-induced osteoporosis (GIOP). Iguratimod (IGU) is a novel conventional synthetic disease-modifying anti-rheumatic drug developed in Japan. The aim of this study is to investigate the effects of IGU on glucocorticoid-induced disorder of bone metabolism in vitro. MATERIALS AND METHODS: In osteoclastogenesis of mouse bone marrow-derived cells, tartrate-resistant acid phosphatase staining, resorption pit assay, western blotting, real-time polymerase chain reaction (PCR), and mRNA sequencing were performed. In osteoblastogenesis of MC3T3-E1 cells, alkaline phosphatase (ALP) staining and activity, alizarin red staining, and mRNA sequencing were performed, and real-time PCR and western blotting were conducted in MC3T3-E1 cells and murine osteocyte-like cell line MLO-Y4 cells. RESULTS: IGU significantly suppressed a dexamethasone-induced increase in osteoclasts, differentiation, and bone resorption activity by inhibition of the receptor activator of the nuclear factor kappa-B (RANK)/tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6)/nuclear factor kappa-B (NFκB)-p52 pathway. In MC3T3-E1 cells, IGU significantly upregulated dexamethasone-induced downregulation of ALP activity, bone mineralization, and osteoblast-related gene and protein expression. In MLO-Y4 cells, IGU significantly upregulated dexamethasone-induced downregulation of the gene expression of ALP and osteocalcin, and also downregulated receptor activator of NFκB ligand (RANKL)/osteoprotegerin gene expression ratio without dexamethasone. CONCLUSION: These results suggest that IGU may improve glucocorticoid-induced disorder of bone metabolism and may exhibit positive effects against GIOP associated with RA.

Effects of follow-on therapy after denosumab discontinuation in patients with postmenopausal osteoporosis.

OBJECTIVES: To clarify the effects of follow-on therapy after denosumab (DMAb) discontinuation. METHODS: In this retrospective, multicenter study, postmenopausal patients with osteoporosis who were previously treated by oral bisphosphonates (BP) (n = 26) or teriparatide (TPTD) (n = 27) were switched to DMAb (administered 2.6 times), and then discontinued. Patients (73.1 years, T-scores of the lumbar spine [LS] - 2.7 and femoral neck [FN] - 2.2) were switched to either (1) raloxifene (RAL) (n = 13) or BP [(2) weekly or monthly BP (wmBP) (n = 29) or (3) zoledronate (ZOL) (n = 11)], based on each physician's decision (mean interval after final DMAb administration was 7.2 months). Bone mineral density (BMD) at final DMAb administration were set as baseline. RESULTS: Changes in LS BMD at 1.5 years after final DMAb administration were -2.7% in the RAL, 0.7% in the wmBP, and 1.9% in the ZOL (p = .31 between groups), and in FN BMD were -3.8%, -0.8%, and 1.8%, respectively (p = .02 between the RAL and ZOL; p = .048 between the RAL and BP). Clinical vertebral fracture incidence during 1.5 years after final DMAb administration was 23.1% in the RAL, 3.4% in the wmBP, and 0.0% in the ZOL (p = .048 between the RAL and ZOL; p = .015 between the RAL and BP). No significant differences were observed in these parameters between the wmBP and ZOL. CONCLUSION: These results may contribute to the selection of adequate follow-on therapy after DMAb discontinuation, although further investigations are required.

A report of three cases which required tibialis anterior tendon resection to recover delayed wound healing after total ankle arthroplasty in patients with rheumatoid arthritis.

Delayed wound healing is one of the severe complications after total ankle arthroplasty (TAA). In particular, once tibialis anterior (TA) tendon is exposed from tendon sheath of extensor retinaculum, wound healing will be critically intractable. We report three cases (mean age: 75.3 years old) of delayed wound healing after TAA cured by resection of TA tendon in patients with rheumatoid arthritis (RA). All three cases underwent TAA through an anterior approach, with careful suture of extensor retinaculum in wound closure. Ankle joint was fixed with splint and avoid weight bearing for three weeks after surgery. Delayed wound healing with TA tendon exposure was observed, and initially treated by debridement, basic fibroblast growth factor spray, and negative pressure wound therapy, which all failed to obtain wound healing. Finally, complete resection of TA tendon led to rapid wound healing. In all cases, ankle dorsal flexion was compensated by other extensors, with maintained range of motion and muscle strength (manual muscle testing 3 to 4) compared to pre-operation at 1 year after TAA operation. Resection of TA tendon may be considered as one of the salvage treatment options of severe delayed wound healing in TAA with anterior approach, especially in elderly patients.

Effects of prior osteoporosis treatment on early treatment response of romosozumab in patients with postmenopausal osteoporosis.

PURPOSE: To investigate the effects of prior treatment and the predictors of early treatment response to romosozumab (ROMO) in patients with postmenopausal osteoporosis. METHODS: In this prospective, observational, multicenter study, 130 treatment-naïve patients (Naïve; n = 37) or patients previously treated with bisphosphonates (BP; n = 33), denosumab (DMAb; n = 45), or teriparatide (TPTD; n = 15) (age, 75.0 years; T-scores of the lumbar spine [LS] -3.2 and femoral neck [FN] -2.9) were switched to ROMO based on their physician's decision. Bone mineral density (BMD) and serum bone turnover markers were evaluated for six months. RESULTS: At six months, LS BMD changes were 13.6%, 7.5%, 3.6%, and 8.7% (P < .001 between groups) and FN BMD changes were 4.2%, 0.4%, 1.6%, and 1.5% (P = .16 between groups) for Naïve, BP, DMAb, and TPTD groups, respectively. Changes in N-terminal type I procollagen propeptide (PINP; µg/L) levels from baseline â†’ one month were 72.7 â†’ 139.0, 33.5 â†’ 85.4, 30.4 â†’ 54.3, and 98.4 â†’ 107.4, and those of isoform 5b of tartrate-resistant acid phosphatase (TRACP-5b) (mU/dL) were 474.7 â†’ 270.2, 277.3 â†’ 203.7, 220.3 â†’ 242.0, and 454.1 â†’ 313.0 for Naïve, BP, DMAb, and TPTD groups, respectively. Multivariate regression analysis revealed that significant predictors of LS BMD change at six months were prior treatment difference (r = -3.1, P = .0027) and TRACP-5b percentage change (r = -2.8, P = .0071) and PINP value at one month (r = 3.2, P = .0021). CONCLUSION: Early effects of ROMO on the increase in LS BMD are significantly affected by the difference of prior treatment and are predicted by the early change in bone turnover markers. MINI ABSTRACT: Early effects of ROMO on the increase in LS BMD at six months is significantly affected by the difference of prior treatment and also predicted by the early change of bone turnover markers in patients with postmenopausal osteoporosis.

Combined effect of teriparatide and an anti-RANKL monoclonal antibody on bone defect regeneration in mice with glucocorticoid-induced osteoporosis.

OBJECTIVE: The purpose of this study was to examine the effect of single or combination therapy of teriparatide (TPTD) and a monoclonal antibody against the murine receptor activator of nuclear factor κB ligand (anti-RANKL Ab) on cancellous and cortical bone regeneration in a mouse model of glucocorticoid-induced osteoporosis (GIOP). METHODS: C57BL/6 J mice (24 weeks of age) were divided into five groups: (1) the SHAM group: sham operation + saline; (2) the prednisolone (PSL) group: PSL + saline; (3) the TPTD group: PSL + TPTD; (4) the Ab group: PSL + anti-RANKL Ab; and (5) the COMB group: PSL + TPTD + anti-RANKL Ab (n = 8 per group). With the exception of the SHAM group, 7.5 mg of PSL was inserted subcutaneously into mice, to generate a mouse model of GIOP. Four weeks after insertion, bone defects with a diameter of 0.9 mm were created to assess bone regeneration on both femoral metaphysis (cancellous bone) and diaphysis (cortical bone). After surgery, therapeutic intervention was continued for 4 weeks. Saline (200 µl) or TPTD (40 µg/kg) was injected subcutaneously five times per week, whereas the anti-RANKL Ab (5 mg/kg) was injected subcutaneously once on the day after surgery. Subsequently, the following analyses were performed: microstructural assessment of bone regeneration and bone mineral density (BMD) measurement via micro-computed tomography, and histological, histomorphometrical, and biomechanical analyses with nanoindentation. RESULTS: The COMB group showed the highest lumbar spine BMD increase (vs. the PSL, TPTD, and Ab groups). The volume of regenerated cancellous bone at the bone defect site was higher in the COMB group compared with the PSL, TPTD, and Ab group. The volume of the regenerated cortical bone was significantly higher in the COMB group compared with the PSL group, and its hardness was significantly higher in the COMB group compared with the PSL and TPTD groups. CONCLUSION: In a mouse model of glucocorticoid-induced osteoporosis, the combination therapy of TPTD plus the anti-RANKL Ab increased bone mineral density in the lumbar spine and regenerated cancellous bone volume compared with single administration of each agent, and also increased regenerated cortical bone strength compared with single administration of TPTD.