Life Course Epidemiology of Hip Osteoarthritis in Japan: A Multicenter, Cross-Sectional Study.

BACKGROUND: The incidence of developmental dysplasia of the hip (DDH) in Japanese newborns has reduced drastically following a primary prevention campaign initiated around 1972 to 1973; this perinatal education campaign promoted maintaining the hips of newborns in the naturally flexed-leg position. The purpose of the present study was to describe the life course epidemiology of hip osteoarthritis (OA) in adolescent and adult patients and to assess its association with exposure to the primary prevention campaign for DDH. METHODS: We included new patients with hip OA diagnosed from January 1, 2022, to December 31, 2022, at 12 core hospitals (8 special-function hospitals and 4 regional medical care support hospitals). The trend in the percentage of hips with a history of DDH treatment in childhood was estimated with use of a centered moving average using the birth year of the patient. We compared the prevalence of severe subluxation (Crowe type II, III, or IV) between patients with secondary hip OA due to hip dysplasia who were born in or before 1972 and those who were born in or after 1973. RESULTS: Overall, 1,095 patients (1,381 hips) were included. The mean age at the time of the survey was 63.5 years (range, 15 to 95 years). A total of 795 patients (1,019 hips; 73.8% of hips) were diagnosed with secondary OA due to hip dysplasia. Approximately 13% to 15% of hips among patients born from 1963 to 1972 had a history of DDH treatment in childhood; however, the percentage decreased among patients born in or after 1973. The prevalence of severe subluxation (Crowe type II, III, or IV) among patients born in or after 1973 was 2.4%, which was significantly less than that among patients born in or before 1972 (11.1%; odds ratio, 0.20; p < 0.001). CONCLUSIONS: As of 2022, secondary hip OA due to hip dysplasia is still responsible for most new cases of adolescent and adult hip OA seen in core hospitals in Japan. However, the perinatal education campaign initiated 50 years ago, which utilized a population approach and advocated for maintaining the hips of newborns in the naturally flexed-leg position, may have improved the environmental factors of DDH, as indicated by the apparently reduced need for treatment of DDH in childhood and the associated severe subluxation. This may result in a reduced need for challenging hip surgery later in life. LEVEL OF EVIDENCE: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.

Vitamin D status-associated postoperative complications in patients with hip dysplasia after periacetabular osteotomy: A case-control study.

OBJECTIVES: This study aimed to clarify the relationship between vitamin D status and complications after periacetabular osteotomy. METHODS: A total of 46 hips of 39 patients (3 men and 36 women; mean age at surgery, 41.0 years; mean postoperative follow-up duration, 63 months) were reviewed to obtain the following information: patients' serum 25-hydroxyvitamin D [25(OH)D] status, prevalence of postoperative delayed union of osteotomy sites in the greater trochanter (DUGT) and ischiopubic stress fractures (IPSFs), and risk factors. RESULTS: The mean serum 25(OH)D level was 11.9 ng/ml. DUGT and IPSF were found in four (10.3%) and three (7.7%) patients, respectively. Serum 25(OH)D levels ≤ 11 ng/ml were significantly associated with DUGT in female patients (p = .02). Serum 25(OH)D levels ≤ 9 ng/ml and smoking were significantly associated with IPSF (p = 0.01 and 0.02, respectively). Overall, 21.7% of patients with serum 25(OH)D levels ≤ 11 ng/ml developed at least one complication; no complications occurred when serum 25(OH)D levels were >11 ng/ml. CONCLUSION: Severe vitamin D deficiency was highly prevalent in relatively young patients. Vitamin D deficiency and smoking were independent risk factors for postoperative complications. Proactive supplementation is advisable to reduce postoperative complications, especially in patients with serum 25(OH)D levels ≤ 11 ng/ml.

Proximal femoral morphology after transtrochanteric posterior rotational osteotomy for osteonecrosis of the femoral head: A three-dimensional simulation study.

BACKGROUND: Transtrochanteric posterior rotational osteotomy (PRO) is one of the joint-preserving surgeries for osteonecrosis of the femoral head. In general, postoperative femoral neck-shaft varus realignment is planned to obtain a sufficient intact articular surface of the femoral head in the weight-bearing portion. Unlike anterior rotational osteotomy, PRO allows for more than 90° rotation of the femoral head, resulting in more complicated morphology. However, little is known about the potential risk of postoperative femoral retroversion after PRO. This simulation study aims: 1) to assess whether postoperative femoral neck-shaft varus realignment can coexist with preserved femoral anteversion after PRO, 2) and whether postoperative proximal femoral morphology could be predicted with approximation equations. HYPOTHESIS: High degree (>90°) PRO is favourable for femoral neck-shaft varus realignment, but unfavourable for maintaining postoperative femoral anteversion. MATERIALS AND METHODS: PRO was simulated by using CT data from 10 hips in 10 healthy volunteers. During simulation, the intertrochanteric osteotomy plane was determined three-dimensionally based on anteroposterior-view line (the osteotomy line on anteroposterior view) and lateral-view line (the osteotomy line on lateral view). By changing either the angle of anteroposterior-view line or lateral-view line, we simulated 90°, 110°, 130° and 150° PRO. To clarify the effects of various posterior rotation angles on postoperative proximal femoral morphology, we made simplified PRO models through changing only the posterior rotation angle. RESULTS: In the 90°, 110°, 130° and 150° PRO models, the vertically inclined angle of anteroposterior-view line showed a significant positive correlation with femoral neck-shaft varus realignment (90° PRO, r=0.90; 110° PRO, r=0.95; 130° PRO, r=0.97; 150° PRO, r=0.99), while a significant negative correlation with postoperative femoral anteversion angle (90° PRO, r=-0.97; 110° PRO, r=-0.95; 130° PRO, r=-0.92; 150° PRO, r=-0.7). Likewise, the posteriorly tilted angle of lateral-view line showed a significant negative correlation with both femoral neck-shaft varus realignment (90° PRO, r=-0.81; 110° PRO, r=-0.81; 130° PRO, r=-0.79; 150° PRO, r=-0.72) and postoperative femoral anteversion angle (90° PRO, r=-0.90; 110° PRO, r=-0.89; 130° PRO, r=-0.92; 150° PRO, r=-0.88). In the simplified PRO models, the posterior rotation angle showed a significant positive correlation with femoral neck-shaft varus realignment (r=0.33), while a significant negative correlation with postoperative femoral anteversion angle (r=-0.76). The approximation equations for predicting the proximal femoral morphology after PRO were validated. DISCUSSIONS: It was confirmed that high-degree PRO (>90°) is favourable for femoral neck-shaft varus realignment, but works against preserving femoral anteversion. With the approximation equations developed in the current study, surgeons could examine the feasibility of PRO based on postoperative femoral anteversion. In terms of hip joint function and subsequent total hip arthroplasty, excessive deformities including femoral retroversion and severe varus deformity could be avoided. LEVEL OF EVIDENCE: IV; case series without control group.

Quantitative evaluation of bone-resorptive lesion volume in osteonecrosis of the femoral head using micro-computed tomography.

Objectives To quantify the volume of bone-resorptive lesions in post-collapse osteonecrosis of the femoral head (ONFH) using micro-computed tomography (micro-CT) and assess their characteristics in post-collapse ONFH. Methods We investigated 35 femoral heads resected from 35 patients with ONFH (20 men and 15 women; mean age, 47.2 years). On each of seven coronal high-resolution micro-CT slices of the femoral head, the bone-resorptive areas were extracted using bone microstructure measurement software. Next, the total bone-resorptive volume ratio, defined as the ratio of all bone-resorptive cross-sectional areas to all femoral head cross-sectional areas in all seven slices, was calculated. Associations between total bone-resorptive volume ratio and sex, age, ONFH-associated factors, patient workload levels, ONFH stage, ONFH type, necrotic volume on magnetic resonance imaging, and duration from the onset of pain to surgery were analyzed. Lesion location and the association between bone-resorptive lesion and collapse were also evaluated. Results The mean total bone-resorptive volume ratio was 7.0±6.0%, which varied significantly by ONFH stage (ARCO collapse quantitation 3A, 3.5±2.1%; 3B, 6.8±3.0%; and 3C, 13.6±8.8%). ONFH stage was independently associated with total bone-resorptive volume ratio (P<0.05). Furthermore, high bone-resorptive volume ratios were found in the anterior femoral head and were associated with collapse. Conclusions This study demonstrated that bone-resorptive volume in post-collapse ONFH was significantly associated with the disease stage, which was more widespread in the anterior portion of the femoral head than in the posterior portion.

Differences in magnetic resonance findings between symptomatic and asymptomatic pre-collapse osteonecrosis of the femoral head.

PURPOSE: The purpose of this study was to assess the differences in magnetic resonance (MR) findings between the symptomatic and asymptomatic pre-collapse stage of osteonecrosis of the femoral head (ONFH). MATERIALS AND METHODS: This study reviewed 123 consecutive hips in 91 patients in the pre-collapse stage of ONFH based on plain radiographic findings. These 123 hips were divided into symptomatic and asymptomatic groups according to the pain domain score in the Harris hip score system. Bone marrow edema (BME), synovial fluid effusion, and subchondral fracture were evaluated using MR imaging. Odds ratios (ORs) were calculated between these three parameters and symptoms. The subsequent clinical course after MR examination was also assessed for each hip that could be followed more than 1 year. RESULTS: Forty-six hips (37.4%) were categorized as symptomatic and 77 hips (62.6%) as asymptomatic. The prevalence of BME, synovial fluid effusion, and subchondral fracture were 87.0% (40/46), 80.4% (37/46), and 34.8% (16/46), respectively, in the symptomatic group, and 0%, 28.6% (22/77), and 0%, respectively, in the asymptomatic group, indicating significant differences between the two groups (p < 0.0001). Among these parameters, BME showed the highest OR with regard to the presence or absence of symptoms (BME, 965.8; joint effusion, 10.3; subchondral fracture, 83.9). Due to persistent pain and subsequent collapse, 30 of 35 (85.7%) symptomatic hips with BME subsequently underwent surgical treatment at a mean interval of 3.47 months after MR examination, while 25 of 66 (37.9%) asymptomatic hips without BME underwent surgical treatment at a mean interval of 20.7 months after MR examination. CONCLUSIONS: This study demonstrated that symptomatic pre-collapse ONFH diagnosed based on plain radiographic findings could be distinguished from asymptomatic pre-collapse ONFH by the presence of BME on MR imaging, and thus BME may be a sign of occult fracture.

Osteonecrosis of the femoral head associated with pigmented villonodular synovitis.

A 23-year-old Japanese woman with no history of corticosteroid intake or alcohol abuse presented with a 10-month history of left hip pain without any antecedent trauma. An anteroposterior radiograph performed 10 months after the onset of pain showed slight joint space narrowing and bone erosions surrounded by sclerotic lesions in both the acetabular roof and femoral neck. Magnetic resonance images of the left hip showed a feature of osteonecrosis of the femoral head and a mass with villus proliferation extending from the posterior intertrochanteric area to the anteromedial aspect of the femoral neck. In addition, the left quadratus femoris muscle, which is generally located just above the nutrient vessels of the femoral head, was not detected. Based on these findings, the patient was diagnosed with osteonecrosis of the femoral head caused by impairment of the nutrient vessels from invasion of the pigmented villonodular synovitis. She underwent radical synovectomy of the left hip 16 months after the onset of pain, and her hip pain improved after the surgery.

Effects of the dynein inhibitor ciliobrevin on the flagellar motility of sea urchin spermatozoa.

Ciliobrevin has recently been found to be a membrane-permeable inhibitor that is specific to AAA+ molecular motors such as cytoplasmic dyneins. In this study, we investigated how ciliobrevin inhibited the motility of sperm from sea urchins: Hemicentrotus pulcherrimus, Pseudocentrotus depressus, and Anthocidaris crassispina. After application of 100 µM of ciliobrevin A to live spermatozoa, swimming speed decreased gradually and flagellar motion stopped almost completely within 5 to 10 min. This inhibition was reversible and the frequency of flagellar beating was reduced in a concentration-dependent manner. Ciliobrevin had similar inhibitory effects on the flagellar beating of demembranated and reactivated sperm and the sliding disintegration of trypsin-treated axonemes. We also analyzed the curvature and shear angle of the beating flagella and found that the proximal region of the sperm flagellum was less sensitive to ciliobrevin compared with more distal regions, where bending motions were blocked completely. Interestingly, the shear angle analysis of flagellar motility showed that ciliobrevin induced highly asymmetric bends in the proximal region of the flagellum. These results suggest that there is heterogeneity in the inhibitory thresholds of dynein motors, which depend on the regions along the flagellar shaft (proximal or distal) and on the sites of doublets in the flagellar cross-section (doublet numbers). We expect that it will be possible to map the functional differences in dynein subtypes along and/or around the cross-sections of flagellar axonemes by analyzing the inhibitory effects of ciliobrevin.

Tubulin-dynein system in flagellar and ciliary movement.

Eukaryotic flagella and cilia have attracted the attention of many researchers over the last century, since they are highly arranged organelles and show sophisticated bending movements. Two important cytoskeletal and motor proteins, tubulin and dynein, were first found and described in flagella and cilia. Half a century has passed since the discovery of these two proteins, and much information has been accumulated on their molecular structures and their roles in the mechanism of microtubule sliding, as well as on the architecture, the mechanism of bending movement and the regulation and signal transduction in flagella and cilia. Historical background and the recent advance in this field are described.

Peptide-induced hyperactivation-like vigorous flagellar movement in starfish sperm.

Asterosap, a sperm-activating peptide (SAP) from the starfish egg jelly coat, is diffusible and controls a cGMP-signalling pathway in starfish sperm in the same manner as resact, a potent chemoattracting SAP in sea urchins. This fact suggests that asterosap may serve as a chemoattractant like resact at concentrations with appropriate gradients. Since asterosap is one of three egg jelly components, which in concert induce the acrosome reaction, it is still worthwhile to evaluate how asterosap modulates sperm motility prior to this reaction. We analysed the flagellar movement of sperm of the starfish Aphelasterias japonica in artificial seawater (ASW) containing the asterosap isoform P15 at 1 micromol l(-1). We found that sperm swim straighter with more symmetrical flagellar movement in P15 than in ASW, but without any significant difference in the flagellar beat frequency and the swimming velocity. The flagellar movement is, however, dramatically different between sperm firmly attached to the solid surface by the head in P15 and those attached in ASW: in P15 the flagellum bends to a greater extent, with higher curvature and with higher shear angle up to a right angle to the flagellar wave axis, and beats at an increased frequency. The vigorous flagellar movement of sperm, which can be activated when sperm are placed in high-load circumstances just as entering into a jelly layer, may increase propulsive forces and hydrodynamic resistances, allowing sperm to undergo the acrosome reaction as effectively as possible.

Roles of cAMP in regulating microtubule sliding and flagellar bending in demembranated hamster spermatozoa.

To understand the mechanism regulating spermatozoa motility, it is important to investigate the mechanism regulating the conversion of microtubule sliding into flagellar bending. Therefore, we analyzed microtubule sliding and its conversion into flagellar bending using a demembranated spermatozoa model in which microtubule sliding and flagellar bending could be analyzed separately by treating the demembranated spermatozoa with and without dithiothreitol, respectively. Using this model, we examined the roles of cAMP and its target molecules in regulating flagellar bending and microtubule sliding. Although flagellar bending did not occur in the absence of cAMP, microtubule extrusion occurred without it, suggesting that cAMP is necessary for the conversion of microtubule sliding into flagellar bending, but not for microtubule sliding itself. The target of cAMP for regulating flagellar bending was not cAMP-dependent protein kinase (PKA), since flagellar bending was still observed in the spermatozoa treated with a PKA-specific inhibitor. Alternatively, the Epac/Rap pathway may be the target. Epac2 and Rap2 were detected in hamster spermatozoa using immunoblotting. Since Rap2 is a GTPase, we investigated the flagellar bending of demembranated spermatozoa treated with GTPgammaS. The treatment markedly increased the beat frequency and bending rate. These results suggest that cAMP activates the Epac/Rap pathway to regulate the conversion of microtubule sliding into flagellar bending.

A sea urchin egg jelly peptide induces a cGMP-mediated decrease in sperm intracellular Ca(2+) before its increase.

Speract, a sperm-activating peptide (SAP) from sea urchin eggs, increases the intracellular concentration of Ca(2+) ([Ca(2+)]i) and modulates sperm motility. We measured the initial sperm response to speract using its caged analog and observed, for the first time, a small but significant decrease in sperm [Ca(2+)]i before the increase. Both directions of the [Ca(2+)]i change were completely blocked in high K(+) seawater. Using membrane-permeant caged cyclic nucleotides (cNMP), only cGMP induced the decrease in [Ca(2+)]i although both cGMP and cAMP increased the [Ca(2+)]i. The decrease in the [Ca(2+)]i induced by cGMP was more notable following a second photolytic event, once [Ca(2+)]i had been elevated by an initial flash. This pattern of [Ca(2+)]i change was confirmed in individual sperm. These results together with pharmacological evidence suggest that the initial [Ca(2+)]i decrease is due to a Na(+)/Ca(2+) exchanger activity, stimulated by hyperpolarization mediated by K(+) efflux through cGMP-regulated K(+) channels.