The impact of chronic obstructive pulmonary disease on bone strength.

Chronic obstructive pulmonary disease (COPD) is a lifestyle-related disease that develops in middle-aged and older adults, often due to smoking habits, and has been noted to cause bone fragility. COPD is a risk factor for osteoporosis and fragility fracture, and a high prevalence of osteoporosis and incidence of vertebral fractures have been shown in patients with COPD. Findings of lung tissue analysis in patients with COPD are primarily emphysema with a loss of alveolar septal walls, and the severity of pulmonary emphysema is negatively correlated with thoracic spine bone mineral density (BMD). On the other hand, epidemiological studies on COPD and fracture risk have reported a BMD-independent increase in fracture risk; however, verification in animal models and human bone biopsy samples has been slow, and the essential pathogenesis has not been elucidated. The detailed pathological/molecular mechanisms of musculoskeletal complications in patients with COPD are unknown, and basic research is needed to elucidate the mechanisms. This paper discusses the impacts of COPD on bone strength, focusing on findings in animal models in terms of bone microstructure, bone metabolic dynamics, and material properties.

DAIR in treating chronic PJI after total knee arthroplasty using continuous local antibiotic perfusion therapy: a case series study.

BACKGROUND: Antimicrobial agents are administered via intramedullary antibiotic perfusion (iMAP)/intrasoft tissue antibiotic perfusion (iSAP) to infected lesions to control osteoarticular and soft tissue infections. Continuous local antibiotic perfusion (CLAP) has been reported to be useful. This study aimed to investigate the outcomes of DAIR combined with CLAP for chronic PJI after total knee arthroplasty performed at our hospital. SUBJECTS AND METHODS: Six patients (male; one case, female; five cases, mean age 79.5 years (70-94)) underwent CLAP for chronic PJI after TKA at our hospital between July 2020 and June 2022. They were followable for at least one year after surgery. Seven months (17-219), with a mean follow-up of 24.3 months (12-36). In addition to direct debridement and insert exchange, systemic antimicrobial treatment, and CLAP with gentamicin were performed using NPWT. We investigated the organisms causing the inflammation, the duration of iMAP/iSAP implantation, the maximum daily dose of GM, the maximum GM blood concentration, and the presence or absence of GM-induced adverse events. RESULT: Two of six patients had a recurrence of infection at five weeks and five months after initial CLAP and required repeat CLAP treatment, but all patients could preserve their components. The organisms responsible for the flare-ups were MSSA in three cases: ESBL-producing E. coli, mixed MSSA and streptococcal infection, Klebsiella pneumonia in one case each, and unknown pathogens in one case. CLAP therapy for all patients was administered eight times in 6 cases: iMAP, mean: 10.0 days (5-16); iSAP, mean: 19.3 days (15-28); GM dose, mean: 162.5 mg/day (80-240); and GM blood concentration, mean: 1.4 µg/mL (0.2-5.0). Adverse events included one case of reversible acute kidney injury during CLAP in a patient with recurrent infection. DAIR with CLAP for chronic post-TKA infection can be a useful treatment option to preserve components and allow the infection to subside, provided the implant is not markedly loosened.

Nitric oxide synthase contributes to the maintenance of LTP in the oxytocin-mRFP1 neuron of the rat hypothalamus.

Oxytocin (OXT) is a neuropeptide hormone that plays a critical role in nociception. Long-term potentiation (LTP) is a major form of synaptic plasticity in the central nervous system. Recently, LTP has been reported in the hypothalamus; however, data on LTP in hypothalamic OXT-ergic neurons are unclear. Furthermore, the signaling pathways for hypothalamic OXT-ergic neuronal LTP and its physiological significance remain unknown. Herein, we aimed to investigate the induction of hypothalamic OXT-ergic neuronal LTP and its synaptic mechanism using OXT-monomeric red fluorescent protein 1 transgenic rats to visualize and record from OXT-ergic neurons. The hypothalamic paraventricular nucleus (PVN) OXT-ergic neuronal LTP induced by the pairing protocol was dependent on N-methyl-D-aspartate receptor (NMDAR). Furthermore, nitric oxide synthase (NOS) is required to maintain the LTP regardless of the NMDARs. In addition, hypothalamic OXT-ergic neuronal LTP was not induced in the adjuvant arthritis rat model but increased excitatory postsynaptic currents were detected. LTP in hypothalamic OXT-ergic neurons in the PVN in the presence of NOS may be involved in neuronal changes during OXT synthesis in chronic inflammation.

Chemogenetic Activation of Oxytocin Neurons Improves Pain in a Reserpine-induced Fibromyalgia Rat Model.

Fibromyalgia (FM) is a syndrome characterized by chronic pain with depression as a frequent comorbidity. However, efficient management of the pain and depressive symptoms of FM is lacking. Given that endogenous oxytocin (OXT) contributes to the regulation of pain and depressive disorders, herein, we investigated the role of OXT in an experimental reserpine-induced FM model. In FM model, OXT-monomeric red fluorescent protein 1 (OXT-mRFP1) transgenic rats exhibited increased depressive behavior and sensitivity in a mechanical nociceptive test, suggesting reduced pain tolerance. Additionally, the development of the FM-like phenotype in OXT-mRFP1 FM model rats was accompanied by a significant reduction in OXT mRNA expression in the magnocellular neurons of the paraventricular nucleus. OXT-mRFP1 FM model rats also had significantly fewer tryptophan hydroxylase (TPH)- and tyrosine hydroxylase (TH)-immunoreactive (ir) neurons as well as reduced serotonin and norepinephrine levels in the dorsal raphe and locus coeruleus. To investigate the effects of stimulating the endogenous OXT pathway, rats expressing OXT-human muscarinic acetylcholine receptor (hM3Dq)-mCherry designer receptors exclusively activated by designer drugs (DREADDs) were also assessed in the FM model. Treatment of these rats with clozapine-N-oxide (CNO), an hM3Dq-activating drug, significantly improved characteristic FM model-induced pathophysiological pain, but did not alter depressive-like behavior. The chemogenetically induced effects were reversed by pre-treatment with an OXT receptor antagonist, confirming the specificity of action via the OXT pathway. These results indicate that endogenous OXT may have analgesic effects in FM, and could be a potential target for effective pain management strategies for this disorder.

Adiponectin inhibits fibrosis of the palmar aponeurosis in Dupuytren's contracture in male patients.

Aims: Dupuytren's contracture is characterized by increased fibrosis of the palmar aponeurosis, with eventual replacement of the surrounding fatty tissue with palmar fascial fibromatosis. We hypothesized that adipocytokines produced by adipose tissue in contact with the palmar aponeurosis might promote fibrosis of the palmar aponeurosis. Methods: We compared the expression of the adipocytokines adiponectin and leptin in the adipose tissue surrounding the palmar aponeurosis of male patients with Dupuytren's contracture, and of male patients with carpal tunnel syndrome (CTS) as the control group. We also examined the effects of adiponectin on fibrosis-related genes and proteins expressed by fibroblasts in the palmar aponeurosis of patients with Dupuytren's contracture. Results: Adiponectin expression in the adipose tissue surrounding the palmar aponeurosis was significantly lower in patients with Dupuytren's contracture than in those with CTS. The expression of fibrosis-related genes and proteins, such as types 1 and 3 collagen and α-smooth muscle actin, was suppressed in a concentration-dependent manner by adding AdipoRon, an adiponectin receptor agonist. The expression of fibrosis-related genes and proteins was also suppressed by AdipoRon in the in vitro model of Dupuytren's contracture created by adding TGF-ß to normal fibroblasts collected from patients with CTS. Conclusion: Fibrosis of the palmar aponeurosis in Dupuytren's contracture in males may be associated with adiponectin expression in the adipose tissue surrounding the palmar aponeurosis. Although fibroblasts within the palmar aponeurosis are often the focus of attention when elucidating the pathogenesis of Dupuytren's contracture, adiponectin expression in adipose tissues warrants closer attention in future research.

Validity and application of Doiguchi's pelvic tilt measurement method.

BACKGROUND: The validity of Doiguchi's pelvic tilt measurement method has not been proven. The objective in our study was to validate the method. METHODS: Our investigation included 73 total hip arthroplasties (THAs) performed using our cup placement procedure from July 2020 to November 2021. Pelvic tilt formed by the pubic symphysis and sacral promontory (PTPS) in supine and lateral positions was calculated by two methods (the Doiguchi method and the digital reconstructed radiograph (DRR) method using a 3D computer templating system) based on the transverse and longitudinal diameters of the pelvic ring measured immediately before THA. RESULTS: There was a strong/moderate correlation in the values of PTPS between the Doiguchi and DRR methods. However, the value of PTPS calculated by the Doiguchi method was significantly lower than that calculated by DRR, and there was a partially direct match. On the other hand, there was no significant difference in the value of PT change from supine to lateral position between the Doiguchi and DRR methods. The PT changes based on both methods were strongly correlated, and the PT change calculated by the Doiguchi method was almost identical to that calculated by the DRR method. CONCLUSIONS: Doiguchi's pelvic tilt measurement method was validated for the first time. These results demonstrated that the ratio of the transverse and longitudinal diameters of the pelvic ring was an important factor defining the change in pelvic tilt. The slope in the linear function of the Doiguchi method was found to be almost the correct value, although the intercept of the linear function exhibited individual differences.

Decrease in osteoporotic fracture in the western Kitakyushu region by the STOP-Fx study.

INTRODUCTION: The Seamless Treatment of Osteoporosis against Fractures (STOP-Fx) study was initiated to provide and continue therapeutic interventions for registered patients with osteoporotic fractures. MATERIALS AND METHODS: Women who visited six hospitals in the western Kitakyushu area for osteoporotic fractures between October 2016 and December 2018 were included in the study. Data collection for primary and secondary outcomes was conducted from October 2018 to December 2020, 2 years after STOP-Fx study enrollment. The primary outcome included the number of surgeries for osteoporotic fractures after the STOP-Fx study intervention, while secondary outcomes were the intervention rate of osteoporosis treatment, incidence and timing of secondary fractures, and factors associated with secondary fractures and loss to follow-up. RESULTS: Concerning the primary outcome, the number of surgeries for osteoporotic fractures decreased since the STOP-Fx study initiation: 813 in 2017, 786 in 2018, 754 in 2019, 716 in 2020, and 683 in 2021. Regarding the secondary outcome, of the 805 patients enrolled, 445 were available for follow-up at 24 months. Of the 279 patients who were untreated for osteoporosis at enrollment, 255 (91%) were on treatment at 24 months. There were 28 secondary fractures, which were associated with increased tartrate-resistant acid phosphatase-5b and decreased lumbar spine bone mineral density during enrollment in the STOP-Fx study. CONCLUSION: As the demographics and medical area served by six hospitals in the western Kitakyushu region have not changed significantly since the STOP-Fx study initiation, the STOP-Fx study may have contributed in decreasing the number of osteoporotic fractures.

Delayed cortical bone healing due to impaired nuclear Nrf2 translocation in COPD mice.

The effect of the pathogenesis of chronic obstructive pulmonary disease (COPD) on bone fracture healing is unknown. Oxidative stress has been implicated in the systemic complications of COPD, and decreased activity of Nrf2 signaling, a central component of the in vivo antioxidant mechanism, has been reported. We investigated the process of cortical bone repair in a mouse model of elastase-induced emphysema by creating a drill hole and focusing on Nrf2 and found that the amount of new bone in the drill hole was reduced and bone formation capacity was decreased in the model mice. Furthermore, nuclear Nrf2 expression in osteoblasts was reduced in model mice. Sulforaphane, an Nrf2 activator, improved delayed cortical bone healing in model mice. This study indicates that bone healing is delayed in COPD mice and that impaired nuclear translocation of Nrf2 is involved in delayed cortical bone healing, suggesting that Nrf2 may be a novel target for bone fracture treatment in COPD patients.

Comparison of gender differences in health-related quality of life between patients with hand disease and those with other musculoskeletal disorders of the knee and lumbar spine.

BACKGROUND: Musculoskeletal diseases are a major public health concern among older adults. There has been an increase in the number of studies on pain between men and women, such as knee and lumbar pain. However, there is a dearth of research on pain between men and women in hand disease. This study compared health-related quality of life (HRQOL) between patients with musculoskeletal disorders of the hand and those with disorders of the knee and the lumbar spine. METHODS: From 2014 to 2018, 5595 adult patients completed a questionnaire on HRQOL. Among these patients, we identified patients with hand disease (n = 1038), knee disease (n = 680), and lumbar spine disease (n = 2021) resulting in a total sample of 3739 patients (1749 men and 1992 women). Patients' responses to the EuroQol (EQ-5D), the Short Form 12-item Survey (SF-12), and three visual analogue scales (VAS), as different measures of the HRQOL, were evaluated. RESULTS: It was found that the EQ-5D index was lowest in the lumbar spine patients, followed by knee and hand patients. The VAS scores were negatively affected in all groups. The EQ-5D index was significantly lower in women than in men only in the hand disease group. Multivariate analysis revealed that for the EQ-5D index, age, gender, and VAS scores for job and activities of daily living were explanatory factors in the hand disease group. Gender was not a significant predictor in the other groups. CONCLUSIONS: This study demonstrated that pain negatively affected HRQOL, and gender differences in HRQOL were found only in patients with hand disease. Gender differences in HRQOL in patients with hand disease warrant appropriate clinical attention.

The Impact of Carpal Tunnel Release on Two-Point Discrimination, Quick Disabilities of Arm, Shoulder and Hand Score and Distal Motor Latency - A Multi-centre Prospective Study.

Background: The authors conducted a prospective, multi-centre study to assess the impact of carpal tunnel release (CTR) on Two-Point Discrimination (2-PD), Quick Disabilities of Arm, Shoulder and Hand Score (Q-DASH), and Distal Motor Latency (DL). The primary aim was to determine the change in outcome measurements (2-PD, Q-DASH and DL) preoperatively and postoperatively at 6 months and 1 year. The secondary aims of the study were to determine whether the postoperative outcomes were different at the 6-month and 1-year follow-up and if there was difference in outcomes based on the preoperative severity of carpal tunnel syndrome (CTS). Methods: A total of 205 hands in 171 patients underwent CTR at five hospitals over a 2-year period. A total of 110 hands in 94 patients were followed-up and analysed. The 2-PD, Q-DASH and DL were measured for all patients preoperatively and at 6 months and 1 year postoperatively. Patients were divided into two groups 'mild' and 'severe' based on pre-operative DL score (mild ≤ 8.1 msec). The change in preoperative and postoperative 2-PD, Q-DASH and DL values were compared. The change in pre-operative and post-operative 2-PD and Q-DASH values were also compared between the 'mild' and 'severe' groups. Results: The 2-PD, Q-DASH and DL showed significant improvement at 6-month and 1-year follow-ups compared to pre-operative values. However, there were no significant differences in all three parameters between the 6-month and 1-year measurements. There was significant improvement in preoperative and postoperative 2-PD and Q-DASH scores between the mild and severe groups. Conclusions: CTR is an effective treatment for patients with CTS with significant improvement in all three outcome parameters (2-PD, Q-DASH and DL). The improvement in outcome plateaus at 6 months and additional follow-up may not be useful. Level of Evidence: Level II (Therapeutic).

Trabecular Bone Volume Is Reduced, With Deteriorated Microstructure, With Aging in a Rat Model of Duchenne Muscular Dystrophy.

We aimed to clarify the effect of aging on trabecular bone volume and trabecular bone microstructure in a rat model of Duchenne muscular dystrophy (DMD). Six rats each of wild type (WT) and DMD model at 15 weeks of age, and 4 rats each at 30 weeks of age, were analyzed by dual energy X-ray absorptiometry and by micro-CT for analysis of trabecular and cortical bone of the femur. Bone mineral density was significantly lower in the DMD group than in the WT group at both 15 and 30 weeks of age. Micro-CT showed that trabecular bone volume and number were not significantly different between the two groups at 15 weeks, but at 30 weeks both were significantly lower in the DMD group than in the WT group. Connectivity density and structure model index were not significantly different between the two groups at 15 weeks, but at 30 weeks they differed significantly. No significant differences between the WT and DMD groups in cortical thickness and cortical area were evident at both 15 and 30 weeks. In conclusion, trabecular bone volume is significantly reduced, with deteriorated microstructure, with aging in a rat model of DMD.

Assessment of influences of posterior rotation of the tibial condyles on the Insall-Salvati ratio.

The positional relationship between patellar and femoral articular surfaces may vary according to the degree of posterior rotation of the tibial condyle, which may influence the patellar configuration. We hypothesized that the configuration of the patella has a rhomboid transformation similar to that of the tibial condyle. This cohort study included 313 patients with knee pain who underwent lateral-view knee digital radiography. The length of the long axis, short axis of the patella, and patellar tendon length of the patellofemoral joint were measured. The patella axis ratio (length of long/short axis) as patellar configuration and Insall-Salvati ratio were calculated. Correlations between the configuration of the tibial condyle and the three length parameters and the Insall-Salvati ratio were assessed. Posterior rotation and the rhomboid transformation of the tibial condyle were positively correlated with the length of the long axis of the patella and negatively correlated with the Insall-Salvati ratio. The more the tibial articular surface shifted posteriorly due to posterior rotation and rhomboid transformation of the tibial condyle, the longer the long axis of the patella was, and the smaller the Insall-Salvati ratio was. The long axis of the patella became longer due to rhomboid transformation, similar to the tibial condyle.

Oxidative stress causes muscle structural alterations via p38 MAPK signaling in COPD mouse model.

INTRODUCTION: Sarcopenia is a complication of Chronic Obstructive Pulmonary Disease (COPD) that negatively affects physical activity and quality of life. However, the underlying mechanism by which COPD affects skeletal muscles remains to be elucidated. Therefore, we investigated the association between oxidative stress and structural alterations in muscles in elastase-induced emphysema mouse models. MATERIALS AND METHODS: Twelve-week-old male C57BL/6J mice were treated with either intratracheal porcine pancreatic elastase (PPE) dissolved in saline, or saline alone. The mice were euthanized 12 weeks after treatment, and the lungs and limb muscles were used for protein analysis of oxidative stress, p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway and muscle atrophy signaling pathway related with oxidative stress. Furthermore, C57BL/6J mice treated with PPE or saline were analyzed for the effects of oral administration of astaxanthin or p38 inhibitor. RESULTS: The weight of the soleus muscle, proportion of type I muscle fibers, and cross-sectional areas of muscle fibers in the PPE group were lower than those in the control group. Oxidative stress marker levels in the PPE group were elevated in skeletal muscles. The p38 MAPK signaling pathway was activated in the soleus muscles, leading to the activation of the ubiquitin-proteasome system and autophagy. Astaxanthin and p38 inhibitors attenuated alterations in muscle structure through the deactivation of the p38 MAPK signaling pathway. CONCLUSIONS: This study provides first evidence in COPD mouse model that oxidative stress trigger a series of muscle structural changes. Our findings suggest a novel target for sarcopenia in COPD.

Endogenous oxytocin exerts anti-nociceptive and anti-inflammatory effects in rats.

Oxytocin is involved in pain transmission, although the detailed mechanism is not fully understood. Here, we generate a transgenic rat line that expresses human muscarinic acetylcholine receptors (hM3Dq) and mCherry in oxytocin neurons. We report that clozapine-N-oxide (CNO) treatment of our oxytocin-hM3Dq-mCherry rats exclusively activates oxytocin neurons within the supraoptic and paraventricular nuclei, leading to activation of neurons in the locus coeruleus (LC) and dorsal raphe nucleus (DR), and differential gene expression in GABA-ergic neurons in the L5 spinal dorsal horn. Hyperalgesia, which is robustly exacerbated in experimental pain models, is significantly attenuated after CNO injection. The analgesic effects of CNO are ablated by co-treatment with oxytocin receptor antagonist. Endogenous oxytocin also exerts anti-inflammatory effects via activation of the hypothalamus-pituitary-adrenal axis. Moreover, inhibition of mast cell degranulation is found to be involved in the response. Taken together, our results suggest that oxytocin may exert anti-nociceptive and anti-inflammatory effects via both neuronal and humoral pathways.

Hip arthroscopic management for treating a rhythmic gymnast with a large bone cyst at the femoral head in the setting of hip dysplasia-a case report.

Recent literature lacks a clear understanding of how to manage bone cysts associated with hip dysplasia. This article aimed to report a case of hip dysplasia in a rhythmic gymnast surgically managed with arthroscopic retrograde bone grafting, labral repair, cam osteoplasty, double shoelace capsular closure and endoscopic shelf acetabuloplasty. A 20-year-old female college rhythmic gymnast presented complaining of right hip pain and discomfort for the past 2 months. This case report describes the use of the CROSSTRAC guide system to perform retrograde bone grafting to treat the bone cyst at the femoral head arthroscopically. Hip arthroscopic retrograde bone grafting, labral repair, cam osteoplasty, double shoelace capsular closure and endoscopic shelf acetabuloplasty are less invasive and beneficial for the treatment of bone cysts of the femoral head associated with hip dysplasia in symptomatic rhythmic gymnasts.

Upregulation of the hypothalamo-neurohypophysial system and activation of vasopressin neurones attenuates hyperalgesia in a neuropathic pain model rat.

Arginine vasopressin (AVP) is a hypothalamic neurosecretory hormone well known as an antidiuretic, and recently reported to be involved in pain modulation. The expression kinetics of AVP and its potential involvement in the descending pain modulation system (DPMS) in neuropathic pain (NP) remains unclear. We investigated AVP expression and its effects on mechanical and thermal nociceptive thresholds using a unilateral spinal nerve ligation (SNL) model. All rats with SNL developed NP. Intensities of enhanced green fluorescent protein (eGFP) in the supraoptic and paraventricular nuclei, median eminence, and posterior pituitary were significantly increased at 7 and 14 days post-SNL in AVP-eGFP rats. In situ hybridisation histochemistry revealed significantly increased AVP mRNA expression at 14 days post-SNL compared with the sham control group. The chemogenetic activation of AVP neurones significantly attenuated mechanical and thermal hyperalgesia with elevated plasma AVP concentration. These analgesic effects were suppressed by pre-administration with V1a receptor antagonist. AVP neurones increased the neuronal activity of serotonergic dorsal raphe, noradrenergic locus coeruleus, and inhibitory interneurones in the spinal dorsal horn. These results suggest that the hypothalamo-neurohypophysial system of AVP is upregulated in NP and activated endogenous AVP exerts analgesic effects via the V1a receptors. AVP neurones may activate the DPMS.

Accurate cup placement using a portable navigation system during total hip arthroplasty based on pelvic orientation in the lateral decubitus position.

BACKGROUND: We previously proposed an accurate cup placement procedure using a portable navigation system (PNS) for total hip arthroplasty (THA) in the lateral decubitus position; however, the accuracy of our proposed procedure has not been shown, the aim of this study was to demonstrate the accuracy. METHODS: We prospectively analyzed 79 hips treated with primary THA; 40 hips treated until June 2020 were included in the conventional procedure (CP) group, and 39 hips treated from July 2020 were included in the modified procedure (MP) group. In the MP, pelvic orientation is considered to be the set coordinate axes in addition to the CP using the PNS. The accuracy was based on the difference between the navigation record (NR) and postoperative computed tomography measurement. RESULTS: The radiographic inclination (RI) and anteversion (RA) accuracies were 1.55° and 2.14°, respectively, in the MP group and 3.03° and 6.20°, respectively, in the CP group (p < 0.001). The error was within 5° of the NR for both the RI and RA in 34 in the MP group (87.2%) and 14 in the CP group (35.0%) (p < 0.001). The error was within 5° of the target angle (RI 40°, RA 15°) for both the RI and RA in 29 hips in the MP group (74.7%) and 12 in the CP group (30.0%) (p < 0.001). CONCLUSIONS: Our procedure with the consideration of pelvic orientation achieved dramatically improved the accuracy of PNS and was suitable to facilitate accurate cup placement.

The CeCORD-J study on collagenase injection versus aponeurectomy for Dupuytren's contracture compared by hand function and cost effectiveness.

This study compared hand function and the cost-effectiveness of treatment between collagenase Clostridium histolyticum (CCH) injection and limited fasciectomy for patients with Dupuytren's contracture (DC). The CeCORD-J study is a prospective, multicenter, non-randomized controlled, observational study of two parallel groups. Participants were DC patients with multiple affected fingers, including flexion contracture of the proximal interphalangeal (PIP) joint. The primary outcome was the Hand10 score, as a patient-reported outcome measure (PROM). We set secondary outcomes of EQ-5D-5L (QOL) score, degree of extension deficit, and direct cost. Propensity score adjustment was used to balance differences in patient characteristics between groups. Participants comprised 52 patients in the Collagenase group and 26 patients in the Surgery group. There were no significant differences in the Hand10 and QOL scores between the two groups at 26 weeks. Mean direct cost was 248,000 yen higher in the Surgery group than in the Collagenase group. Extension deficit angle of the PIP joint was significantly larger in the Collagenase group at 26 weeks. Although the Collagenase group showed dominance in cost-effectiveness, there was no significant difference between the two groups in hand function at 26 weeks.