Reduced bone formation markers, and altered trabecular and cortical bone mineral densities of non-paretic femurs observed in rats with ischemic stroke: A randomized controlled pilot study

Abstract

BackgroundImmobility and neural damage likely contribute to accelerated bone loss after stroke, and subsequent heightened fracture risk in humans.ObjectiveTo investigate the skeletal effect of middle cerebral artery occlusion (MCAo) stroke in rats and examine its utility as a model of human post-stroke bone loss.MethodsTwenty 15-week old spontaneously hypertensive male rats were randomized to MCAo or sham surgery controls. Primary outcome: group differences in trabecular bone volume fraction (BV/TV) measured by Micro-CT (10.5 micron istropic voxel size) at the ultra-distal femur of stroke affected left legs at day 28. Neurological impairments (stroke behavior and foot-faults) and physical activity (cage monitoring) were assessed at baseline, and days 1 and 27. Serum bone turnover markers (formation: N-terminal propeptide of type 1 procollagen, PINP; resorption: C-terminal telopeptide of type 1 collagen, CTX) were assessed at baseline, and days 7 and 27.ResultsNo effect of stroke was observed on BV/TV or physical activity, but PINP decreased by -24.5% (IQR -34.1, -10.5, p = 0.046) at day 27. In controls, cortical bone volume (5.2%, IQR 3.2, 6.9) and total volume (6.4%, IQR 1.2, 7.6) were higher in right legs compared to left legs, but these side-to-side differences were not evident in stroke animals.ConclusionMCAo may negatively affect bone formation. Further investigation of limb use and physical activity patterns after MCAo is required to determine the utility of this current model as a representation of human post-stroke bone loss.

Sinusoidal Electromagnetic Fields Increase Peak Bone Mass in Rats by Activating Wnt10b/β-Catenin in Primary Cilia of Osteoblasts

“…The ROI for the cortical bone analyses was located at the midpoint between the apex of the femoral head and the base of the condyles and extended 100 slices to the distal end. The cortical bone area (Ct.Ar) and its fraction (Ct. Ar/Tt.Ar) were obtained …”

Does Hip Bone Density Differ between Paretic and Non-Paretic Sides in Hemiplegic Stroke Patients? and Its Relationship with Physical Impairment

“…Only limited information is available from stroke and non-stroke animal models which demonstrated the effects of brain and central nervous system regulation on bone turnover, suggesting that stroke induced neural damage may directly increase bone loss regardless of level of physical activity. [14][15][16][17][18] The majority of the clinical studies that examined the bone properties in stroke patients included both sexes. Previous studies confirmed that the postmenopausal period is the strongest factor affecting the decrease of the BMD, however.…”

Beyond the Brain: The Systemic Pathophysiological Response to Acute Ischemic Stroke

“…Inner ear vestibular lesioning in rats decreased bone formation without affecting resorption or locomotor activity [ 104 ]; these alterations in bone metabolism were attributed to SNS outflow and prevented with β2-adrenergic receptor blockade [ 104 ]. Likewise, serum bone formation marker N-terminal propeptide of type 1 procollagen (PINP) decreased independent of activity level in MCAO rats, with no change in resorption marker C-terminal telopeptide of type I collagen (CTX) [ 105 ]. Further investigation is needed to define exact pathways involved with brain control of bone metabolism and stroke-induced remodeling disorders.…”