The Effectiveness of Leukocyte-Poor Platelet-Rich Plasma Injections for Symptomatic Mild to Moderate Osteoarthritis of the Knee With Joint Effusion or Bone Marrow Lesions in a Japanese Population: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

BACKGROUND: Intra-articular platelet-rich plasma (PRP) injections have been proposed for the treatment of knee osteoarthritis (OA); however, their effectiveness in Japanese patients remains unclear. PURPOSE: To investigate whether 3 intra-articular injections of leukocyte-poor PRP (LP-PRP) improve symptoms and joint function in symptomatic Japanese patients with mild to moderate knee OA. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: Of 72 patients screened, 30 were included and randomized to receive LP-PRP (n = 15) or saline (placebo; n = 15) injections between March 2019 and February 2023. Patients attended a screening visit and 3 treatment visits at 1 week apart, followed by 3 follow-up visits (at 4, 12, and 24 weeks) after the initial treatment visit. The primary efficacy outcome measure was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, whereas the secondary efficacy outcome measures were the proportion of patients showing a visual analog scale (VAS) improvement of ≥50%. Magnetic resonance imaging was performed to evaluate joint effusion and bone marrow lesions using the Whole-Organ Magnetic Resonance Imaging Score. Patients were followed for 24 weeks. RESULTS: Patients in the PRP group (mean age, 65.9 years) had a mean hip-knee-ankle angle of 5.1°, with 7 and 8 patients demonstrating Kellgren-Lawrence grade 2 and 3 knee OA, respectively. Patients in the placebo group (mean age, 67.9 years) had a mean hip-knee-ankle angle of 3.8°, with 6 and 9 patients showing Kellgren-Lawrence grade 2 and 3 knee OA, respectively. No significant differences were identified in any baseline factors. The percentage change in Western Ontario and McMaster Universities Osteoarthritis Index scores from baseline to 24 weeks was significantly different (P= .032) between the PRP (median, 75.9%; quantile 1 [Q1], 49.6; quantile 3 [Q3], 94.1]) and placebo (median, 27.7%; Q1, -9.4; Q3, 80.9]) groups. Overall, 73.3% and 28.6% of the PRP group and placebo group, respectively, exhibited an improvement in visual analog scale scores of ≥50%, with a significant improvement observed in the PRP group (P = .027). Changes in bone marrow lesions from baseline to 24 weeks, as assessed on magnetic resonance imaging, significantly differed between groups (P = .017), with no significant differences in other secondary endpoints. CONCLUSION: In Japanese patients with knee OA, 3 intra-articular LP-PRP injections led to clinical improvements at 24-week follow-up and significant functional improvements and pain relief after 24 weeks.

Varus knee osteoarthritis with ankle osteoarthritis demonstrates greater hindfoot inversion and larger ankle inversion loading during gait following total knee arthroplasty compared to varus knee osteoarthritis alone.

PURPOSE: Although patients with varus knee osteoarthritis (KOA) and concurrent ankle osteoarthritis (AOA) may experience increased ankle joint pain after total knee arthroplasty (TKA), the underlying mechanism remains unclear. This study aimed to investigate the effects of concurrent AOA on ankle and hindfoot alignment, frontal plane ankle and hindfoot biomechanics during gait following TKA and the clinical outcomes. METHODS: Twenty-four patients with varus KOA who underwent TKA were included in this retrospective cohort study. Patients were categorized into two groups: with and without AOA. Radiographic evaluations of lower-limb, ankle and hindfoot alignment, and knee and ankle clinical outcomes were conducted preoperatively and 6 months postoperatively. In addition, gait analyses were performed to investigate knee, ankle and hindfoot kinematics and kinetics. Each data was compared between patients with and without AOA. RESULTS: Concomitant AOA was found in eight ankles. The AOA group exhibited greater postoperative hindfoot varus and increased postoperative ankle pain than the non-AOA group. Gait analysis showed no significant differences in knee varus alignment or tibial tilt after TKA between the groups. However, the AOA group demonstrated significantly greater hindfoot inversion and larger ankle inversion loading. CONCLUSION: One third of patients who underwent TKA had concurrent AOA associated with hindfoot varus. Despite achieving proper coronal knee alignment postoperatively, these patients experienced greater hindfoot and ankle joint inversion load during gait. Surgeons should consider the inability to evert the hindfoot and the possibility of increased ankle joint pain when planning and performing TKA. LEVEL OF EVIDENCE: Level III.

Bisphosphonate-Related Atypical Femoral Fractures in Patients with Autoimmune Disease Treated with Glucocorticoids: Surgical Results for 20 Limbs.

BACKGROUND: Glucocorticoids induce osteoporosis, while bisphosphonates treat it, yet both can lead to atypical femoral fractures. Patients on both agents may face challenges in healing from such fractures due to their pathophysiology and pharmacological effects. METHODS: Intramedullary nail surgery was performed on 20 limbs in 19 patients with atypical femoral fractures and autoimmune diseases, who had received bisphosphonates for GC-induced osteoporosis. The average durations of glucocorticoid and bisphosphonate use were 17 and 9 years (standard deviation: 7.59 and 4.35), respectively, and the mean follow-up period was 66 months. Fifteen and five limbs were fractured at the subtrochanter and diaphysis, respectively. The surgical techniques (type of nail) and additional procedures performed in these cases were examined. The post-operative alignment and reduction status on radiographs were examined to determine their relationship with post-operative outcomes. RESULTS: Cephalomedullary long nails were inserted in nine limbs and antegrade intramedullary nails in 11 limbs. As an additional surgical procedure, open reduction, bone grafting and drilling were carried out on six, two, and five limbs, respectively. Regarding malalignment on radiographs, AP images showed varus in four limbs, and lateral images showed extension in two limbs. Regarding the cortical discontinuity, the distal fragment of the 11th limb shifted posteriorly in the lateral view. Gaps at the fracture sites were observed in 11 limbs. As a result, bone union was confirmed in 13 limbs. Five of the seven nonunion limbs required additional surgery. When comparing union and nonunion, open reduction and drilling were involved in nonunion limbs. CONCLUSION: The surgical outcomes of atypical femoral fractures in patients with autoimmune disease and on long-term glucocorticoids and bisphosphonates were poor. Although it is not possible to affirm for sure based on these results alone, management with prophylactic surgery before complete fracture is considered to be required to improve outcomes.

Does loop length change after anterior cruciate ligament reconstruction with adjustable loop cortical suspension device?: Observation of the hamstring graft completely filling the femoral tunnel.

PURPOSE: The adjustable loop cortical suspension device (ALD) is a useful femoral fixation device in anterior cruciate ligament (ACL) reconstructions, but the possibility of loosening has been suggested. The purpose of this study was to evaluate the elongation of an adjustable loop and the position of the hamstring graft inside the femoral socket. METHODS: The subjects were 33 patients who underwent ACL reconstruction with a hamstring tendon. The graft was fixed using ALD and completely filled the femoral socket. Magnetic resonance images were taken one week and one year after the operation. The loop length, femoral socket length, and graft length inside the socket were measured and statistically compared with the clinical outcomes. RESULTS: The loop length one week after surgery was 18.9 ± 4.4 mm, and 1 year after surgery was 19.9 ± 4.5 mm (P < 0.001). The gap between the top of the graft and femoral socket was 0.9 ± 1.8 mm one week after surgery and 1.3 ± 1.7 mm one year after surgery (P = 0.259). At one week post-operation, a gap was found in nine patients (27.3%). The loop length and gap did not strongly correlate with clinical findings. CONCLUSION: ACL reconstruction using ALD showed a gap between the graft and femoral socket at the one week post-operation mark in 27.3% of participants. One year after the surgery, there were cases where the gap increased and/or decreased, but the elongation of the loop was 1 mm on average. Our findings suggest that ALD is clinically safe to use; however, has the possibility of initial loop elongation and non-uniform changes. LEVEL OF EVIDENCE: IV.

Joint effusion at 3 months after anterior cruciate ligament reconstruction is associated with reinjury.

PURPOSE: To evaluate whether joint effusion at 3 months after anterior cruciate ligament (ACL) reconstruction is associated with ACL reinjury. METHODS: The medical records of 227 consecutive patients who underwent single-bundle ACL reconstruction between 2015 and 2018 were reviewed in this retrospective single-center study. Demographic data such as sex and age at surgery, as well as data on preinjury Tegner activity scale score, time from injury to surgery, presence of meniscus and cartilage injuries, and the occurrence of ACL reinjury within 2 years, were collected. Joint effusion was defined as grade 3 (range 0-3) according to the ACL Osteoarthritis Score by magnetic resonance imaging at 3 months postoperatively. Multivariate logistic regression analysis was performed to control for potential confounders. RESULTS: A total of 176 patients (mean age 22.5 ± 9.9 years) were included. Among these patients, 18 (10.2%) had ACL reinjury. At the multivariate logistic regression analysis, higher Tegner activity scale (odds ratio [OR] 3.12; 95% confidence interval [CI] 1.61-6.04; p < 0.001) and presence of joint effusion (OR 34.5; 95% CI 6.63-179.7; p < 0.001) increased the odds of ACL reinjury, and older age (OR 0.68; 95% CI 0.51-0.92; p = 0.012) decreased the odds of ACL reinjury. CONCLUSIONS: Joint effusion with a larger fluid volume at 3 months postoperatively was one of the risk factors for ACL reinjury independent of confounders, such as age and activity level. This result suggests the possibility of postoperative intervention for ACL reinjury. LEVEL OF EVIDENCE: III.

Relationship Between Posterior Tibial Slope and Lower Extremity Biomechanics During a Single-Leg Drop Landing Combined With a Cognitive Task in Athletes After ACL Reconstruction.

Background: A steeper posterior tibial slope (PTS) is an important risk factor for anterior cruciate ligament (ACL) reinjury. The PTS may affect lower extremity biomechanics under competition-like conditions for athletes with a reconstructed ACL. Hypothesis: It was hypothesized that the PTS would be associated with lower extremity biomechanics, which may increase ACL strain. Study Design: Descriptive laboratory study. Methods: Included were 10 athletes (mean age, 20.9 ± 1.8 years) who had undergone ACL reconstruction. The authors recorded the 3-dimensional lower extremity biomechanics while participants performed a single-leg drop jump with the Stroop task (dual task). Kinematic and kinetic data were analyzed and compared between the involved and contralateral limbs. The medial and lateral PTSs were measured using magnetic resonance imaging scans of the involved knee. The correlation between the biomechanical data and the PTS in each knee was evaluated. Results: The lateral PTS was significantly correlated with the maximum hip adduction moment (r = 0.64; P < .05) and maximum internal tibial rotation angle (r = 0.71; P < .05) in the involved limb. There were no differences in kinematic and kinetic data between the involved and contralateral limbs. Conclusion: In athletes after ACL reconstruction, the lateral PTS was directly associated with the maximum internal tibial rotation angle during single-leg drop landing with a cognitive task. Clinical Relevance: The findings in this study indicate that a steeper lateral PTS may cause internal rotation of the tibia during landing, which may be associated with reinjury in athletes with a reconstructed ACL.

Radiographic analysis using the hip-to-calcaneus line and its association with lower limb joint kinetics in varus knee osteoarthritis.

BACKGROUND: This study aimed to (1) determine whether the hip to ankle (HA) line or hip to calcaneus (HC) line better reflects knee coronal plane kinetics, (2) to examine whether the HC line reflects ankle coronal plane kinetics, and (3) to evaluate the radiological and biomechanical aspects of ankle in varus knee osteoarthritis (OA). METHODS: Full-length, postero-anterior radiographs (hip-to-calcaneus radiographs) were taken and gait analysis was performed in 21 varus knee OA patients. The %HA where the HA lines pass through the tibial plateau, and the %HC and the mechanical ankle joint axis point (MAJAP), where the HC line passes through the tibial plateau and tibial plafond, respectively, were calculated. Knee adduction angular impulse (KAAI) and ankle inversion angular impulse (AIAI) were collected as kinetic data. Finally, we divided the patients into two groups with and without ankle OA, and compared each parameter between both groups. RESULTS: The %HA and %HC were correlated with KAAI (%HA; r = -0.68, P = 0.001, %HC; r = -0.81, P < 0.001, respectively) and MAJAP was correlated with AIAI (r = -0.55, P = 0.009). MAJAP was significantly smaller, and KAAI and AIAI were significantly larger in the ankle OA group. CONCLUSIONS: Radiographic analysis using the HC line was more strongly correlated to knee joint kinetics than the HA line and was also correlated to ankle joint kinetics. Assessing lower limb alignment using the HC line could be useful to evaluate the knee and ankle joints for varus knee OA.

A Retrospective Analysis of Clinical Outcome and Predictive Factors for Responders with Knee Osteoarthritis to a Single Injection of Leukocyte-Poor Platelet-Rich Plasma.

Although various platelet-rich plasma (PRP) kits are commercially available, the efficacy of these kits for knee osteoarthritis (KOA) has not been fully investigated. This study aimed to investigate the short-term results of leukocyte-poor PRP (LP-PRP) and the factors that contribute to its efficacy. We retrospectively reviewed 124 patients with KOA who were treated with LP-PRP. White blood cell (WBC) and platelet counts in the whole blood and the LP-PRP were measured. KOA severity was assessed using radiography. Clinical evaluation was performed both prior to injection and after an average of 3.3 weeks after the injection using the Japanese Knee Osteoarthritis Measure (JKOM). Responders were defined based on the JKOM. The contributing factors for responders were examined using a multivariate logistic analysis. The responder rate was 58.1% and the contributing factors for responders were a higher visual analog scale score before injection, WBC count in whole blood, and platelet concentration ratio of LP-PRP. The LP-PRP improved the clinical scores in the short term. Certain patient characteristics before injection and the concentration ratio of LP-PRP may be predictors of its efficacy; these may provide clues for elucidating which components of LP-PRP act on KOA pathologies.

Feasibility and efficacy of knee extension training using a single-joint hybrid assistive limb, versus conventional rehabilitation during the early postoperative period after total knee arthroplasty.

Objectives: To evaluate the feasibility and efficacy of treatment for the recovery of knee joint function after total knee arthroplasty (TKA) using a robotic suit. Patients and Methods: Knee joint extension exercise sessions were started with a robotic suit (single-joint hybrid assistive limb [HAL-SJ, Cyberdyne, Inc., Tsukuba, Japan]) in one group of patients after TKA. Patients who underwent standard rehabilitation were enrolled in the control group. To evaluate feasibility and safety, we assessed the adverse events, the number of training sessions, and training time. We compared the changes in knee joint pain and extension lag (°) between the groups. Results: The average age was 71.3 ± 6.2 years in the HAL-SJ group and 74.9 ± 8.7 years in the control group. There were no severe adverse events. In the HAL-SJ group, training was performed 2.9 times, on average, and lasted 18.8 min. In the HAL-SJ group, there was a reduction in the visual analog scale (VAS) for pain after training, which was not significant. In the control group, the VAS score worsened after the sessions. The extension lag significantly improved in the HAL-SJ group after the 2nd and 3rd sessions, and this was more due to improvements in their active extension range of motion than their passive extension range of motion. Conclusions: HAL-SJ-based training is safe and effective, and leads to instantaneous improvement of extension lag, without worsening knee joint pain. HAL-SJ-based knee extension training could represent a viable novel post-TKA rehabilitation modality.

A radiological study of bone remodeling with two different types of porous ß-tricalcium phosphate in humans.

In this study we compared the bone remodeling of unidirectional (UDPTCP) and spherical porous ß-tricalcium phosphate (SPTCP) radiologically in humans. We performed a retrospective analysis of the data of 14 patients (sex, nine men and five women; age, 37-70 years) who underwent medial opening-wedge high tibial osteotomy (MOWHTO) and were followed up for 12 months after surgery. Two wedge-shaped ß-TCPs (one UDPTCP and one SPTCP) were cut and placed parallel to each other in the gap. In Group A (eight knees), UDPTCP was implanted anteriorly and SPTCP posteriorly, while in Group B (six knees), SPTCP was implanted anteriorly and UDPTCP posteriorly. Computed tomography (CT) was performed at 1 week, 6 months, and 12 months after surgery, with the CT attenuation values calculated for UDPTCP and SPTCP. In Groups A and B, the CT attenuation values for UDPTCP were significantly lower at 6 and 12 months after surgery compared to those at 1 week (P < 0.05); nevertheless, no statistical difference in the comparison with SPTCP was observed. After a short-term follow-up of 12 months following MOWHTO, UDPTCP provided earlier bone remodeling than SPTCP. This outcome was achieved regardless of the position, anterior or posterior, in the MOWHTO gap.

Gait Analysis Comparing Kinematic, Kinetic, and Muscle Activation Data of Modern and Conventional Total Knee Arthroplasty.

BACKGROUND: To provide normal knee function, a total knee arthroplasty (TKA) implant with an anatomic surface shape and an adequate sagittal position has been developed. However, it is unclear how this modern implant influences knee joint kinetics and muscle activation during a gait. Therefore, we evaluated this modern TKA prosthesis and compared it with a conventional TKA prosthesis for gait analysis in terms of kinetics and muscle activation. METHODS: Subjects were patients (>60 years of age) with knee osteoarthritis who had undergone unilateral TKA. Twelve patients received the modern TKA prosthesis (group modern), and the other 12 patients received a conventional TKA prosthesis (group conventional). The subjects underwent motion capture analyses with a force plate, and kinematic and kinetic data were acquired from a 10-m gait test. Electromyography data of 6 lower limb muscles were simultaneously collected during the gait test. The 2 groups were compared using unpaired t-tests. RESULTS: In group modern, gait speed was faster, step length was longer, and the knee flexion angle during the initial stance phase was larger. Furthermore, in group modern, the maximum knee extension moment was higher; however, the quadriceps muscle activity tended to be lower than that in group conventional. CONCLUSIONS: Gait characteristics of group modern were more like a normal gait, and knee joint extension moments were greater. This finding indicates that the quadriceps muscles can be more effectively activated, and the anterior stability function of the anterior cruciate ligament may be reproduced with the shape of the modern implant.

Surgical results of atypical femoral fractures in long-term bisphosphonate and glucocorticoid users - Relationship between fracture reduction and bone union.

Atypical femoral fracture (AFF) associated with bisphosphonate (BP) use is common, and its pathophysiology is considered to involve severely suppressed bone turnover. Surgical results following AFF fixation have not been optimal, with some cases resulting in delayed union or nonunion. Regarding bone healing, glucocorticoid (GC) has similar properties to BP. We investigated the surgical results of AFF fixation in both users of BP and GC, especially with regard to intraoperative fracture reduction. We included 12 AFFs in 11 patients with a follow-up over one year who all took GC for autoimmune disease and BP for management of GC-induced osteoporosis. Their mean age was 62 years and 10 patients were female. Six fractures were located in the subtrochanteric region of the femur and six were in the diaphysis. Intramedullary nails were used to treat all fractures. Union rate was recorded, and the status of the reduction immediately after the operation was analyzed. Four of the 12 cases developed nonunion, and three of them required additional surgery. The relationship between alignment, cortical continuity, fracture gap, and bone union was not significant. In the nonunion cases, cortical continuity on the anteroposterior and lateral views were never confirmed. Even if cortical continuity in either of the views was there, the two limbs resulted in nonunion. One third of the patients with AFF secondary to long-term BP and GC use developed nonunion despite their fracture reductions being acceptable. We consider strict reduction should be needed for these cases with disadvantage condition to bone union.

Ten-year results of concentrated autologous bone marrow aspirate transplantation for osteonecrosis of the femoral head: a retrospective study.

BACKGROUND: Idiopathic osteonecrosis of the femoral head (ONFH) occurs at a relatively younger age. It is therefore important to prevent the resultant femoral head collapse and requirement of total hip arthroplasty in these patients. In 2003, we initiated concentrated autologous bone marrow aspirate transplantation (CABMAT), a joint-preserving treatment for ONFH, at our institution. Here, we report the long-term results of CABMAT treatment. METHODS: We retrospectively collated and analyzed the demographic and treatment data of 69 patients (109 hips) with idiopathic ONFH treated with CABMAT between April 2003 and April 2008. RESULTS: Totally, 44 patients (21 men, 23 women, 80 hips) completed the 10-year follow-up. The follow-up rate was 73.4%, and the mean follow-up period was 12.0 (range, 10.0-15.4) years. The mean age of the patients was 42.2 (range, 16.3-70.5) years. Using the Association Research Circulation Osseous (ARCO) classification system for preoperative analysis, 12, 31, 32, and 5 hips were classified as stages 1, 2, 3, and 4, respectively. The overall rate of conversion to total hip arthroplasty (THA) was 34% (27/80 hips). In a multivariate regression analysis, the preoperative stage of ONFH and the body mass index were found to correlate significantly with conversion to THA. Totally, 43 hips (of 80) were classified as belonging to the pre-collapse stage (i.e., stages 1 or 2). The overall collapse rate and the THA-conversion rate of these hips were estimated to be 49% (21/43) and 14% (6/43), respectively. CONCLUSIONS: On the basis of our long-term findings, the minimally invasive and feasible CABMAT therapy can be utilized as one of a joint-preserving treatment for ONFH.

Comparative Analysis of Cellular and Growth Factor Composition in Bone Marrow Aspirate Concentrate and Platelet-Rich Plasma.

The purpose of this study was to quantify the stem cell and growth factor (GF) contents in the bone marrow aspirate concentrate (BMAC) and platelet-rich plasma (PRP) prepared from whole blood using a protocol established in our laboratory. We examined 10 patients with osteonecrosis of the femoral head who were treated by autologous BMAC transplantation at our hospital between January 2015 and June 2015. We quantified CD34+ and CD31-CD45-CD90+CD105+ cells in BMAC and PRP by flow cytometry. Additionally, we measured various GFs, that is, basic fibroblast growth factor (b-FGF), platelet-derived growth factor-BB (PDGF-BB), vascular endothelial growth factor (VEGF), transforming growth factor-ß1 (TGF-ß1), and bone morphogenetic protein-2 (BMP-2) in BMAC and PRP using enzyme-linked immunosorbent assays and statistical analyses. CD34+ and CD31-45-90+105+ cells accounted for approximately 1.9% and 0.03% of cells in BMAC and no cells in PRP. The concentration of b-FGF was higher in BMAC than in PRP (P < 0.001), whereas no significant differences in the levels of PDGF-BB, VEGF, TGF-ß1, and BMP-2 were observed between the two types of sample. BMAC had an average of 1.9% CD34+ and 0.03% CD31-45-90+105+ cells and higher levels of b-FGF than those of PRP.

Robotic device-assisted knee extension training during the early postoperative period after opening wedge high tibial osteotomy: a case report.

BACKGROUND: Maintenance or restoration of a good range of motion of the knee is one of the most important outcomes following knee surgery. According to previous studies, opening wedge high tibial osteotomy enables better recovery of range of motion in knee flexion than that achievable after total knee arthroplasty or unicompartmental knee arthroplasty. However, few reports provide a detailed description of the postoperative recovery of knee extension range of motion after opening wedge high tibial osteotomy. We describe our experience with a knee extension training program using a single-joint hybrid assistive limb device (HAL-SJ; Cyberdyne Inc., Tsukuba, Japan) during the acute recovery phase after opening wedge high tibial osteotomy. The HAL-SJ is a wearable robotic device that facilitates voluntary control of knee joint motion. CASE PRESENTATION: A 67-year-old Japanese woman who underwent opening wedge high tibial osteotomy for spontaneous osteonecrosis of the left medial femoral condyle received HAL-SJ-based knee extension training postoperatively. Our experience with this patient revealed that knee extension training with the HAL-SJ during the acute phase following opening wedge high tibial osteotomy is feasible. Furthermore, the patient's knee extension range of motion improved to values similar to those seen during the preoperative stage, and her flexion range of motion was improved at 3 months after the surgery. CONCLUSIONS: HAL-SJ-based knee extension training could be used as a novel post-opening wedge high tibial osteotomy rehabilitation modality. Further exploration of individualized optimal settings of the HAL-SJ is required to improve its safety and efficacy.

Location of fractures and the characteristics of patients with atypical femoral fractures: analyses of 38 Japanese cases.

The purpose of this study was to determine fracture location and the characteristics of patients with atypical femoral fractures (AFFs). We studied 38 AFFs in 34 patients admitted to our institution between November 2007 and July 2013. The diagnostic criteria for the AFFs were based on 2014 American Society of Bone and Mineral Research guidelines. We classified the fracture location as proximal, middle, or distal to trisect the femoral diaphysis from just distal to the lesser trochanter to just proximal to the supracondylar flare. Bowing was defined as a line through the inside of the tip of the great trochanter and a condylar center that was outside the medullary cavity. We investigated the fracture's location, existence of coronal bowing, and bisphosphonates (BPs), glucocorticoids (GCs), and proton pump inhibitors therapy. We analyzed associations between fracture location and demographic and clinical factors. Twelve fractures were proximal, 25 were middle, and one was distal. Nineteen limbs showed femoral bowing. Thirty-one patients received BP treatment-20 patients received alendronic acid, eight risedronic acid, and three minodronic acid. Fourteen patients received a GC, and 16 received a proton pump inhibitor. There was a significant association between coronal bowing and middle fracture locations, GC therapy and proximal fracture locations, and older age and middle fracture locations. Tall height and heavy weight had an association with proximal fracture location, and short height and light weight had an association with middle fracture location. In conclusion, we provide evidence supporting a causal relationship between BP-related severely suppressed bone turnover and AFFs. We also provide evidence supporting additional influences from altered distribution of mechanical stress with femoral bowing and various factors, such as GC therapy, age, body weight, and height, which might negatively affect bone intensity and quality and result in fracture.