Assessment of baseline bone turnover marker levels and response to risedronate treatment: Data from a Japanese phase III trial.

BACKGROUND: Risedronate increases bone mineral density (BMD) and reduces fracture risk, but treatment response may depend on the baseline state of bone turnover. Data regarding the selection of therapeutic drugs or the prediction of therapeutic effects with baseline levels of bone turnover markers (BTMs) as a reference are insufficient. We hypothesized that when the baseline levels of BTMs are higher, baseline BMD might be lower, changes in BMD at 12 months after risedronate treatment might be higher, and the reduction of fracture incidence might be greater. This study aimed to analyze the data of a phase III clinical trial of risedronate from Japan to investigate the relationships between baseline BTM levels and (1) baseline BMD, (2) changes in BMD at 12 months after the start of treatment, and (3) the incidence of new vertebral fractures. METHODS: This post-hoc analysis included 788 postmenopausal women with osteoporosis whose baseline BTM levels as well as baseline and endpoint BMDs were measured. Relationships between baseline BTM levels and BMD at baseline and 12 months after risedronate treatment and new vertebral fractures were examined. One-way analysis of variance, two-tailed Student's t-test, and Fisher's exact test were used to analyze the data. RESULTS: Baseline BMD showed a significant upward trend when baseline BTM levels were lower in the analysis by tertiles. New vertebral fractures tended to occur in patients with prevalent vertebral fractures, but the relationship between new fractures and BTM levels was not statistically significant. Regardless of BTM types, BMD percentage increments (%) and increments (g/cm2) with the 12-month treatment were high when pretreatment BTM levels were high (P < 0.0001), and a >5.0% increase in BMD was observed even if baseline BTM levels were within the normal range. A new vertebral fracture occurred in only six patients (0.77%), and there was not enough statistical power to clarify the relationship between baseline BTM levels and fracture risk reduction. CONCLUSIONS: When pretreatment BTM levels increased, baseline BMD tended to be lower and the increase in BMD with 12-month risedronate treatment was higher. However, BMD could still be increased even if the baseline BTM levels are within the normal range. Combined with available evidence, baseline BTMs may not have an important role in deciding the optimal therapy. To elucidate the relationship between baseline BTM levels and long-term fracture risk, it will be necessary to conduct more large-scale studies with a longer follow-up period in severe osteoporotic patients with a high fracture risk. MINI ABSTRACT: We evaluated the significance of baseline bone turnover markers in the response to risedronate treatment. The increase in the bone mineral density (BMD) with the 12-month treatment may be higher when the state of bone turnover at baseline is higher, and BMD could still be increased even if the baseline bone turnover is within the normal range.

Spontaneous bilateral femoral neck fractures in a young male adult: a case report and literature review.

BACKGROUND: Simultaneous bilateral femoral neck fracture is a very rare condition, even in osteoporotic elderly individuals. We report an atypical case of a young male adult who developed simultaneous bilateral femoral neck fractures without previous trauma or overuse. CASE PRESENTATION: A 33-year-old man presented with discomfort in the bilateral groin, which had started 2 weeks previously. Bilateral femoral neck fractures were observed on a radiograph, and in addition, a fracture line was seen at the right subchondral region of the acetabulum using magnetic resonance imaging (MRI). Although the patient had no obvious risk factors associated with bone fragility, his bone mineral density measured using dual X-ray absorptiometry indicated severe osteoporosis (lumber spine: T score - 3.4 standard deviation [SD]; femoral neck: T score - 2.8 SD). Serum 25-hydroxyvitamin D level was deficient (19 ng/mL), which was considered to be partly due to non-sunlight exposure for 3 years owing to social withdrawal. Bilateral osteosynthesis was performed, considering his young age, although more than 2 weeks had passed since the onset of the fracture. Bone union and non-occurrence of osteonecrosis of the femoral head were confirmed via radiography and MRI 8 months after the surgery. CONCLUSIONS: Our case suggests that simultaneous non-traumatic bilateral femoral neck fractures can occur in healthy young men.

The depth of the low-intensity band on the T1-weighted MR image is useful for distinguishing subchondral insufficiency fracture from osteonecrosis of the collapsed femoral head.

PURPOSE: To verify the hypothesis that depth of the low-intensity band on T1-weighted MR image is useful for distinguishing subchondral insufficiency fracture (SIF) from osteonecrosis of the collapsed femoral head (ON). PATIENTS AND METHODS: We reviewed 35 consecutive hips in 35 patients with radiological evidence of subchondral collapse of the femoral head and available MR images and histology between May 2013 and January 2016. Both clinical and radiological appearances were investigated. The ratios of distance from articular surface of the femoral head to the T1 low-intensity band to femoral head diameter (band depth ratio: BDR) on (1) mid-coronal slice of MR images and that on (2) coronal slice of MR images in which the highest BDR was observed, were calculated. RESULTS: The mean age in SIF group was significantly higher than that in ON group (SIF: 68 years, ON: 49 years, P = 0.0017). The rates of history of steroid intake or alcohol consumption in SIF group were significantly lower than those in ON group (P = 0.0022 and P = 0.0408, respectively). The mean BDRs in SIF group were (1) 0.16 and (2) 0.23, which were significantly lower than those in ON group [(1) 0.42 and (2) 0.59] (P < 0.0001 for both). The cut-off BDR values to differentiate SIF from ON were (1) 0.22 and (2) 0.38, respectively. CONCLUSION: The results of the study suggest that depth of the low-intensity band on T1-weighted MR image is useful for distinguishing SIF from ON in cases with collapsed femoral heads.

Clinical outcomes in relation to locations of bone marrow edema lesions in patients with a subchondral insufficiency fracture of the hip: a review of fifteen cases.

OBJECTIVE: The prognosis of patients with a subchondral insufficiency fracture remains unclear. The purpose of this study was to investigate the correlation between locations of bone marrow edema (BME) lesions and clinical outcome in patients with a subchondral insufficiency fracture of the hip. METHODS: We retrospectively reviewed 15 consecutive hips in 14 patients who were diagnosed with subchondral insufficiency fracture of the hip at our institution between April 2013 and September 2014. This study included five males (six hips) and nine females (nine hips), ranging from 36 to 83 years of age (mean age: 66 years). The mean duration from the onset of hip pain to MRI examination was 1.8 months (range 0.5-5 months). Both clinical and imaging findings were investigated. RESULTS: Based on the findings of MR images, BME lesion in the femoral head alone was observed in six patients (six hips), BME lesion in the acetabulum alone was observed in one patient (two hips) and BME lesions in both the femoral head and acetabulum were observed in seven patients (seven hips). 3 of 15 hips resulted in rapidly destructive arthrosis and their BME lesions were observed in both the femoral head and acetabulum. 8 of 15 hips successfully healed by conservative treatment and BME lesions in 7 of these 8 hips were observed in only the femoral head or acetabulum. CONCLUSION: The results of this study indicate that the locations of BME lesions (femoral side alone, acetabular side alone or both) may be related to the clinical outcome in patients with a subchondral insufficiency fracture of the hip. ADVANCES IN KNOWLEDGE: Patients with subchondral insufficiency fracture of the hip in whom BME lesions were observed in both the femoral head and acetabulum may have a higher risk to need to undergo total hip arthroplasty.

Brown tumor of the patella caused by primary hyperparathyroidism: a case report.

It has been reported that the common sites of brown tumors are the jaw, pelvis, ribs, femurs and clavicles. We report our experience in a case of brown tumor of the patella caused by primary hyperparathyroidism. An initial radiograph and CT showed an osteolytic lesion and MR images showed a mixed solid and multiloculated cystic tumor in the right patella. One month after the parathyroidectomy, rapid bone formation was observed on both radiographs and CT images.

Extension gap needs more than 1-mm laxity after implantation to avoid post-operative flexion contracture in total knee arthroplasty.

PURPOSE: In total knee arthroplasty (TKA), a high soft-tissue tension in extension at the time of operation would cause a post-operative flexion contracture. However, how tight the extension gap should be during surgery to avoid a post-operative flexion contracture remains unclear. The hypothesis is that some laxity in the intraoperative extension gap is necessary to avoid the post-operative flexion contracture. METHODS: A posterior-stabilized TKA was performed for 75 osteoarthritic knees with a varus deformity. The intraoperative extension gap was measured using a tensor device that provides the gap length and the angle between the femoral component and the tibial cut surface. The medial component gap was defined as the gap calculated by subtracting the selected thickness of the tibial component, including the polyethylene liner, from the extension gap at the medial side. Then, the patients were divided into three groups according to the medial component gap, and post-operative extension angle measured 1 year after the surgery was compared between each groups. RESULTS: One year post-operatively, a flexion contracture of more than 5° was found in 0/34 patients when the medial component gap was more than 1 mm, in 2/26 (8%) patients when the gap was between 0 and 1 mm, and in 3/15 (20%) patients when the gap was <0 mm. Three factors were associated significantly with the post-operative extension angle: age, preoperative extension angle, and medial component gap. CONCLUSION: The intraoperative extension gap is related to the post-operative extension angle. Surgeons should leave more than 1-mm laxity after the implantation to avoid the post-operative flexion contracture. As a clinical relevance, this study clarified the optimal extension gap to avoid the post-operative flexion contracture. LEVEL OF EVIDENCE: Prospective comparative study, Level II.

Medial sixth of the patellar tendon at the tibial attachment is useful for the anterior reference in rotational alignment of the tibial component.

PURPOSE: The anteroposterior (AP) axis connecting the middle of the posterior cruciate ligament to the medial border of the patellar tendon at its attachment has been introduced as a reproducible and reliable reference perpendicular to the surgical epicondylar axis in healthy knees. A recent literature has reported that the AP axis of the tibia is, on average, almost perpendicular to the surgical epicondylar axis also in varus and valgus knees and can be used as a tibial rotational reference to minimize the risk for rotational mismatch between the femoral and tibial components in total knee arthroplasty (TKA). However, it is difficult to identify the AP axis after tibial resection. The purpose of the current study was to determine a modified AP axis that runs parallel to the AP axis and passes through the centre of the cut surface in osteoarthritic knees. METHODS: Preoperative computed tomography scans on 30 varus and 30 valgus knees undergoing TKA were studied using a three-dimensional software. The modified AP axis that runs parallel to the AP axis and passes through the centre of the cut surface was drawn. We investigated where the modified AP axis crossed the patellar tendon at its tibial attachment. RESULTS: The modified AP axis passed through the medial 1/6 of the patellar tendon (4 mm from medial edge) at its attachment in both varus and valgus knees. CONCLUSIONS: The AP axis of the tibia is useful as a tibial rotational reference in cutting the proximal tibia, but it is difficult to identify the AP axis after tibial resection. The clinical relevance of this study is that medial 1/6 of the patellar tendon at its attachment would be a useful landmark in aligning the tibial component. LEVEL OF EVIDENCE: IV.

Lateral soft tissue laxity increases but medial laxity does not contract with varus deformity in total knee arthroplasty.

BACKGROUND: In TKA, soft tissue balance (the joint gap) depends on the amount of resected bone and soft tissue release. Some studies report preoperative bony deformity correlates with soft tissue balance evaluated intraoperatively and that the medial tissues are contracted with varus deformity. However, these studies did not take into account the amount of resected bone and did not describe whether the soft tissue was tight or loose. Therefore, it remains unclear whether in varus deformity the soft tissues on the medial side are contracted. QUESTIONS/PURPOSES: We compared (1) intraoperative joint gap, (2) amount of resected bone, and (3) intraoperative soft tissue laxity on the lateral and medial sides according to severity of preoperative varus deformity. METHODS: We retrospectively reviewed 70 patients with osteoarthritis and varus deformities who underwent 90 TKAs. We retrospectively divided the 90 knees into three groups according to degree of preoperative alignment: mild varus group (<10°), moderate varus group (10°-20°), and severe varus group (>20°). To evaluate intraoperative soft tissue tension, we calculated the soft tissue gap by subtracting the thickness of the resected bone from the joint gaps on the medial and lateral sides, respectively. We then explored the relationship between the soft tissue gap and preoperative alignment. RESULTS: The lateral soft tissue gap was larger in the severe varus group than in the mild and moderate varus groups. The medial soft tissue gap was larger in the severe varus group than in the mild varus group, but there were no differences in the medial joint gaps among the groups. CONCLUSIONS: After the bone is resected, the soft tissue on the lateral side is more lax; however, the soft tissue on the medial side is not shorter with greater preoperative varus deformity.

Relationship between the tibial anteroposterior axis and the surgical epicondylar axis in varus and valgus knees.

PURPOSE: Proper rotational alignment in total knee arthroplasty (TKA) is essential for successful outcomes. The surgical epicondylar axis (SEA) has been frequently used to determine the femoral rotational alignment, and the anteroposterior (AP) axis of the tibia described in previous study has been introduced as a line perpendicular to the SEA in healthy knees. However, the rotational relationship between the distal femur and the proximal tibia would vary between normal and osteoarthritic knees, and a question remains whether the rotational relationship between the SEA and the AP axis of the tibia would be the same between normal and osteoarthritic knees. This study aims to determine whether the AP axis of the tibia is actually perpendicular to the SEA and useful for the tibial rotational alignment also in osteoarthritic knees. METHODS: Preoperative computed tomography scans on 25 varus and 25 valgus knees undergoing TKA were studied. The SEA and the AP axis of the tibia were identified using a three-dimensional software, and the angle between the line perpendicular to the projected SEA and the AP axis was measured. RESULTS: The AP axis of the tibia was 1.7° ± 4.3° and 2.0° ± 4.0° internally rotated relative to the line perpendicular to the SEA in the varus and valgus groups, respectively. CONCLUSIONS: The AP axis of the tibia was, on average, perpendicular to the SEA in both varus and valgus knees. The AP axis would be useful for setting the tibial component with minimal rotational mismatch. LEVEL OF EVIDENCE: IV.

Anterior border of the tibia as a landmark for extramedullary alignment guide in total knee arthroplasty for varus knees.

A disadvantage to using extramedullary alignment guides of the tibia for total knee arthroplasty (TKA) is difficulty in correctly identifying the ankle center. The anterior border of the tibia is easily palpable, as it is not covered by muscles and its shape is convex anteriorly. We hypothesized that appropriate points exist along the anterior border that can be used as landmarks for extramedullary guides. Prior to TKA, computed tomographic images of the entire tibia were obtained from 101 osteoarthritic knees with varus deformities. The relationship between the lines connecting two points on the anterior border and the mechanical axis was evaluated using 3D imaging software. The mean angles between each of 10 determined axes and the mechanical axis varied from 3.2° varus to 2.1° valgus in the coronal plane. In the sagittal plane, all axes referencing the anterior border of the tibia showed anterior inclination to the mechanical axis. The line connecting the medial one-third of the patellar tendon attachment and the distal one-fourth of the anterior border, however, was highly consistent and parallel to the mechanical axis in the coronal plane. This axis can be effectively used as a landmark for extramedullary guides during TKA.

Flexion contracture persists if the contracture is more than 15° at 3 months after total knee arthroplasty.

After total knee arthroplasty, it is common for flexion contracture to exist during the early stages of postoperative course. We retrospectively investigated whether the early postoperative contracture would finally disappear, in 104 osteoarthritic knees after surgery with posterior-stabilized prostheses. The knees were divided into 5 groups based on their contracture 3 months after surgery (group I: no contracture, group II: 5°, group III: 10°, group IV: 15°, group V: ≥20°). The proportion of patients with residual contracture (≥5°) 2 years after surgery was 1/34 in group I, 4/30 in group II, 6/23 in group III, 6/6 in group IV, and 11/11 in group V. The results show that flexion contracture eventually existed if the contracture was more than 15° 3 months after surgery.

Accuracy of image-free navigation for severely deformed knees.

This study evaluated the accuracy of an image-free navigated total knee arthroplasty (TKA) system when used to align deformed tibia bone models. The accuracy was assessed in normal, 10 degrees varus, 20 degrees varus, 10 degrees valgus, and 20 degrees valgus tibia bone models (a total of five tibial models) by direct measurement of the navigated cutting guide. The mean angular errors in the tibial mechanical axes of the normal, 10 degrees, and 20 degrees varus models, respectively, were 0.0 degree, 0.7 degree varus, and 2.4 degrees varus. Thus, the errors seen with the two varus models were significantly larger than that associated with the normal model. The mean angular errors were 0.1 degree varus and 0.4 degree valgus in the 10 degrees and 20 degrees valgus models, respectively. These errors were not significantly different from those obtained with the normal model. These results suggest that in varus-deformed knees, image-free navigation has a tendency to cut the tibia in varus. This fact is considered to be one of the reasons for the lack of superiority of TKA alignment in severely deformed knees when using image-free navigation. Therefore, special attention must be paid when using image-free navigation TKA in such cases.