Effects of hindlimb suspension on development of proximal and distal femur morphological abnormalities in growing rats

Abstract

Although morphological abnormalities of the femur are known predisposing factors for numerous musculoskeletal disorders, the etiology of these abnormalities is poorly understood. This study aimed to investigate whether femoral morphogenesis is affected by hindlimb suspension (HS) in growing rats. We used 41 four‐week‐old female rats in this study. In the HS groups, rats were suspended from their tails for 2, 4, and 8 weeks. Age‐matched animals were used as controls. We examined morphological indices of the femur using three‐dimensional reconstructed images from X‐ray computed tomography. The femoral neck anteversion angle (AVA) was higher with growth in the experimental groups and did not differ in control groups. The AVAs in the HS groups were larger than controls at any time point. In the control groups, the trochlear angle (TA) was higher, rotating inward with growth, but did not differ in the HS groups. The TAs in the HS groups were smaller and rotated more outward compared with the control groups at any time point. The height ratios of the medial and lateral condyles (MC/LC), an asymmetry index, were larger in the HS groups compared to controls at any time point. There were strong relationships between proximal (AVA) and distal morphologies, such as the TA (Spearman's coefficient [rs] = −0.80, p < 0.001) and MC/LC (rs = 0.79, p < 0.001). Our data suggest that sufficient physical activity in early life may protect against morphological femur abnormalities associated with hip and knee joint diseases.

Development of patellofemoral osteoarthritis with knee joint malalignment and lateral patellar dislocation after hindlimb suspension in growing rats

“…A previous study demonstrated that the effect of unloading on the formation of femur morphologies was associated with numerous musculoskeletal disorders, including patellar instability and dislocation. 9 This is the first report to provide the evidence that reduced mechanical stress on joints during the growth phase may be an Data indicate the number of knee joints that were positive for each parameter divided by the total number of knees (upper) and incidence rate (lower).…”

“…In the HS groups, HS was performed for 2, 4, or 8 weeks as previously described with slight modifications. 9 Briefly, rats aged 4 weeks in both groups were anesthetized via intraperitoneal injection of ketamine (60 mg/kg) and xylazine (8 mg/kg). In the HS groups, a Kirschner wire was transversely inserted into the rat tail.…”

“…Using X-ray computer tomography (CT) image analysis, it was shown that hindlimb suspension (HS) in growing rats alters distal femoral morphologies, including trochlear angle and lateral trochlear inclination. 9 Trochlear angle is closely associated with patellar tilt angle (an index of PF malalignment). 10 Lateral trochlear inclination is also associated with increased TT-TG distance in patients with patellar instability.…”

“…11 Furthermore, HS resulted in an increase in the femoral neck anteversion angle. 9 Increased femoral neck anteversion is closely associated with anterior knee pain, 12 PF instability, 13 and knee OA. 12 These findings suggest that inadequate joint loading during growth interferes with the structural stability of the PF joint and induces PFOA.…”

Hindlimb Unloading Induces Bone Microarchitectural and Transcriptomic Changes in Murine Long Bones in an Age-Dependent Manner

“…Alternatively, the 7 μm voxel size that we used may not be sufficient resolution to observe the presence of thin trabeculae, at which point, nanoCT may be required to visualize changes. However, trabecular bone is important for transmitting forces throughout the anatomy of the bone, and so it would logically decrease in the context of disuse, but not aging [34,35].…”