Inhibitory effect of ribbon-type NF-κB decoy oligodeoxynucleotides on osteoclast induction and activity in vitro and in vivo

In this study we examined the effect of ribbon-type (circular-type) NF-κB decoy oligodeoxynucleotides (RNODN) on osteoclast induction and activity. We extracted bone marrow cells from the femurs of rats and incubated non-adherent cells with receptor activator of nuclear factor κB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). First, transfer efficiency into osteoclasts and their precursors, resistance to exonuclease, and binding activity of decoy to NF-κB were examined. Next, to examine the effect of RNODN on osteoclast induction and activity, osteoclast differentiation and pit formation assays were performed. RNODN were injected into the ankle joints of rats with collagen-induced arthritis. Joint destruction and osteoclast activity were examined by histological study. The resistance of RNODN to exonuclease and their binding activity on NF-κB were both greater than those of phosphorothionated NF-κB decoy oligodeoxynucleotides. The absolute number of multinucleate cells scoring positive for tartrate-resistant acid phosphatase was significantly decreased in the RNODN-treated group. The average calcified matrix resorbed area was significantly decreased in the RNODN-treated group. Histological study showed marked suppression of joint destruction and osteoclast activity by intra-articular injection of RNODN. These results suggest the inhibitory effect of RNODN on the induction and activity of osteoclasts. Direct intra-articular injection of RNODN into the joints may be an effective strategy for the treatment of arthritis

Comparison of a self-administered foot evaluation questionnaire (SAFE-Q) between joint-preserving arthroplasty and resection-replacement arthroplasty in forefoot surgery for patients with rheumatoid arthritis

Objectives: To clarify the difference of patient-based outcome between joint-preserving arthroplasty and resection-replacement arthroplasty in forefoot surgery for patients with rheumatoid arthritis (RA). Methods: A total of 63 feet of 49 RA patients who underwent forefoot surgery were asked to answer pre-operative and post-operative self-administered foot evaluation questionnaire (SAFE-Q). Patients were treated with either (1) metatarsal head resection-replacement arthroplasty (28 feet, post-operative mean age 63.8 years, follow-up 4.2 years, DAS28-CRP 2.2) or (2) metatarsophalangeal joint-preserving arthroplasty (35 feet, post-operative mean age 63.1 years, follow-up 3.6 years, DAS28-CRP 2.1) at each surgeon’s discretion. Results: Mean pre-operative and post-operative subscale scores of SAFE-Q of group (1) and (2) were as follows. Pain and pain-related [(1) pre-op 36.8 to post-op 75.0 vs. (2) pre-op 42.2 to post-op 82.6], physical functioning and daily-living [(1) 43.2–68.8 vs. (2) 52.778.1], social functioning [(1) 44.3–72.0 vs. (2) 52.5–81.9], general health and well-being [(1) 48.4–68.4 vs. (2) 45.5–84.4], and shoe-related [(1) 30.1–50.3 vs. (2) 30.6–64.4]. Both general health and well-being subscale scores (p < 0.05) and shoe-related subscale scores (p < 0.05) were significantly more improved in group (2) compared with group (1). Conclusions: Joint-preserving arthroplasty resulted in better patient-based outcomes than resection-replacement arthroplasty.Ebina K., Hirao M., Hashimoto J., et al. Comparison of a self-administered foot evaluation questionnaire (SAFE-Q) between joint-preserving arthroplasty and resection-replacement arthroplasty in forefoot surgery for patients with rheumatoid arthritis. Modern Rheumatology 27, 795 (2017); https://doi.org/10.1080/14397595.2016.1259968

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 → one month were 72.7 → 139.0, 33.5 → 85.4, 30.4 → 54.3, and 98.4 → 107.4, and those of isoform 5b of tartrate-resistant acid phosphatase (TRACP-5b) (mU/dL) were 474.7 → 270.2, 277.3 → 203.7, 220.3 → 242.0, and 454.1 → 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.Ebina K., Hirao M., Tsuboi H., et al. Effects of prior osteoporosis treatment on early treatment response of romosozumab in patients with postmenopausal osteoporosis. Bone 140, 115574 (2020); https://doi.org/10.1016/j.bone.2020.115574

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.Ebina K., Tsuboi H., Nagayama Y., et al. Effects of prior osteoporosis treatment on 12-month treatment response of romosozumab in patients with postmenopausal osteoporosis. Joint Bone Spine 88, 105219 (2021); https://doi.org/10.1016/j.jbspin.2021.105219

Additional file 1: of Expression and pathological effects of periostin in human osteoarthritis cartilage

Primer list for qRT-PCR. (XLSX 10 kb

Modified Anterolateral Approach for Total Ankle Arthroplasty

Level of Evidence: Level V