Regional modular responses in different bone compartments to the anabolic effect of PTH (1-34) and axial loading in mice.

Beneficial effects of intermittent parathyroid hormone (PTH) on bone mass and architecture are described to either simply add to, or to synergise with those of mechanical loading. We evaluate whether interaction with in vivo loading is reinforced by PTH dosing regimen and exhibits compartment-specific sensitivities. Female 12-week-old C57Bl6 mice received daily (7/7) or interrupted 5 day/week (5/7) PTH for 3 weeks (two vehicle groups). All mice had six loading episodes (12N) applied to right tibia (left, non-loaded) for the last 2 weeks. Micro-CT scans were used to evaluate mass and architecture in almost the entire cortical and proximal trabecular regions. Epiphyseal cortical, trabecular and marrow space volumes, and bony growth-plate bridge incidence were evaluated. Statistical analyses employed a linear mixed-effects model at each percentile and 2-way ANOVA with post-hoc test for epiphyses and bridging. We found that daily PTH enhances cortical mass and modifies shape along almost the entire tibia and that these effects are partly mitigated by brief interruption in treatment. Mechanical loading alone augments cortical mass and modifies shape but only in a region proximal to the tibiofibular junction. The effect of combining load and daily PTH dosing is solely additive for cortical bone mass with no significant load: PTH interaction, but exhibits clear synergy with interrupted PTH treatment. Daily, not interrupted PTH stimulates trabecular bone gains, yet load:PTH interaction is present at limited regions with both daily and interrupted treatment. PTH treatment, but not loading, modifies epiphyseal bone but, in contrast, only loading modifies bridge number and areal density. Our findings demonstrate impressive local effects on tibial mass and shape of combined loading and PTH that are sensitive to dosing regimen and exert their effects modularly. These findings emphasise a need to clarify PTH dosing regimens and that advantages could be accrued by aligning treatment accordingly to patient requirements and life-style.

An examination of two different approaches for the study of femoral neck fracture: Towards a more relevant rodent model.

Femoral neck fractures are a massive personal and health programme burden. Methods to study femoral neck strength, across its combined trabecular and cortical components are therefore essential. Rodent ovariectomy-induced osteoporosis models are commonly coupled with ex vivo 3-/4-point bending methods to measure changes in femoral cortical diaphysis. The loading direction used to assess these properties are often non-physiologic and, moreover, these ovariectomy models are linked to marked weight gain that can influence the biomechanical properties. Herein, we explore whether more physiological axial ex vivo loading protocols applied to femoral neck samples of ovariectomised (OVX) rodents provide anatomically-relevant models for the assessment of strength. We examine the use of mouse and rat femurs, loaded in constrained and unconstrained configuration, respectively, and explore whether weight-correction increases their utility. Accordingly, the mid-shaft of the proximal half of femurs from OVX and sham-operated (Sham) mice was methacrylate-anchored and the head loaded parallel to the diaphysis (constrained). Alternatively, femurs from OVX and Sham rats were isolated intact and axially-loaded through hip and knee joint articular surfaces (unconstrained). Yield displacement, stiffness, maximum load and resilience were measured and fracture pattern classified; effects of body weight-correction via a linear regression method or simple division were assessed. Our data reveal significant deficiencies in biomechanical properties in OVX mouse femurs loaded in constrained configuration, only after weight-correction by linear regression. In addition, evaluation of rat femur biomechanics in unconstrained loading demonstrated greater variation and that weight-correction by simple division improved scope to reveal significant OVX impact. We conclude that greater femoral neck fracture susceptibility can indeed be measured in OVX rodents as long as multiple biomechanical parameters are reported, care is taken in choosing the method for assessing load-bearing strength and weight-correction applied. These studies advance the establishment of more relevant rodent models for the study of femoral neck fracture.

Sciatic neurectomy-related cortical bone loss exhibits delayed onset yet stabilises more rapidly than trabecular bone.

Disuse osteoporosis occurs after extended periods of bed rest or nerve damage leading to increased risk of fracture. It remains to be established, however, whether the trajectory of bone loss is equivalent in bone's cortical and trabecular compartments following long-term periods of reduced loading. Herein, we evaluate sciatic neurectomy-related cortical and trabecular bone loss in the tibia by microCT. The right hind limb of seventeen 12 week-old female mice was subjected to sciatic neurectomy (right, SN; left, contralateral internal control) and the animals were sacrificed in four groups (n = 3-5/group) at 5, 35, 65 and 95 days thereafter. Cortical bone mass, geometry and mineral density were evaluated along almost the entire tibial length and trabecular bone was examined at the proximal metaphysis. We found that trabecular bone volume (BV/TV) and number were decreased within 5 days, with a trajectory of loss that only plateaued after 65 days post-SN. In contrast, decreases in cortical thickness, cross-sectional area, second moment of inertia along minor and major axes and predicted resistance to torsion were unmodified during the early 5 day period, attaining significance only after 35 days post-SN and, thereafter showed no further deterioration. Only cortical ellipticity and periosteal enclosed area, continued to change in the SN limbs (vs. contralateral) between 35 and 95 days along the tibia length. On the other hand, cortical tissue mineral density was unmodified by SN at any time point. These data indicate that SN-related cortical bone loss extends along almost the entire tibia, exhibits delayed onset and yet stabilises its architecture more rapidly than trabecular bone. These data suggest that the cortical and trabecular compartments behave as distinct modules in response to SN even within an individual bone.

Long-term bisphosphonate treatment coupled with ovariectomy in mice provokes deleterious effects on femoral neck fracture pattern and modifies tibial shape.

AIMS: The processes linking long-term bisphosphonate treatment to atypical fracture remain elusive. To establish a means of exploring this link, we have examined how long-term bisphosphonate treatment with prior ovariectomy modifies femur fracture behaviour and tibia mass and shape in murine bones. METHODS: Three groups (seven per group) of 12-week-old mice were: 1) ovariectomized and 20 weeks thereafter treated weekly for 24 weeks with 100 µm/kg subcutaneous ibandronate (OVX+IBN); 2) ovariectomized (OVX); or 3) sham-operated (SHAM). Quantitative fracture analysis generated biomechanical properties for the femoral neck. Tibiae were microCT scanned and trabecular (proximal metaphysis) and cortical parameters along almost its whole length measured. RESULTS: Fracture analyses revealed that OVX+IBN significantly reduced yield displacement (vs SHAM/OVX) and resilience, and increased stiffness (vs SHAM). OVX+IBN elevated tibial trabecular parameters and also increased cortical cross-sectional area and second moment of area around minor axis, and diminished ellipticity proximally. CONCLUSION: These data indicate that combined ovariectomy and bisphosphonate generates cortical changes linked with greater bone brittleness and modified fracture characteristics, which may provide a basis in mice for interrogating the mechanisms and genetics of atypical fracture aetiology.Cite this article: Bone Joint Open 2020;1-9:512-519.

Evaluation of intraluminal pressure in cystorrhaphies with and without intestinal serosal patch supplementation from canine cadavers.

PURPOSE: To evaluate the maximal intraluminal pressure (MIP) supported by canine cadaveric urinary bladders that underwent cystotomy followed by cystorraphy, with and without serosal patching-supplementation. METHODS: Two groups (n=8 each) were formed, and in one (conventional) the cystotomy was closed with cushing pattern. In the other group (serosal), the same procedure was performed, and a piece of jejunum was used for the construction of the serosal patching over the cystorraphy. MIP was measured by means of an invasive blood pressure transducer with closed stopcock attached to a multiparameter monitor. At the end of each measurement, the bladder body circumference was assessed. RESULTS: Mean ± SD MIP sustained for the conventional and serosal groups were 28.88 ± 5.08 and 65.38 ± 10.99 mmHg, respectively (p < 0.0001). Bladder circumference did not change significantly between groups (p = 0.35) and did not correlate with MIP assessed in conventional (p = 0.27; r = 0.4379) and serosal groups (p = 0.37; r = -0.3637). CONCLUSION: Serosal patch-supplemented cystorraphies were able to sustain intraluminal pressures 55.8% higher, than nonsupplemented cystorraphies in specimens from canine cadavers.

Evaluation of intraluminal pressure in cystorrhaphies with and without intestinal serosal patch supplementation from canine cadavers

PURPOSE:To evaluate the maximal intraluminal pressure (MIP) supported by canine cadaveric urinary bladders that underwent cystotomy followed by cystorraphy, with and without serosal patching-supplementation.METHODS:Two groups (n=8 each) were formed, and in one (conventional) the cystotomy was closed with cushing pattern. In the other group (serosal), the same procedure was performed, and a piece of jejunum was used for the construction of the serosal patching over the cystorraphy. MIP was measured by means of an invasive blood pressure transducer with closed stopcock attached to a multiparameter monitor. At the end of each measurement, the bladder body circumference was assessed.RESULTS:Mean±SD MIP sustained for the conventional and serosal groups were 28.88±5.08 and 65.38±10.99 mmHg, respectively (p<0.0001). Bladder circumference did not change significantly between groups (p=0.35) and did not correlate with MIP assessed in conventional (p=0.27; r=0.4379) and serosal groups (p=0.37; r=-0.3637).CONCLUSION:Serosal patch-supplemented cystorraphies were able to sustain intraluminal pressures 55.8% higher, than nonsupplemented cystorraphies in specimens from canine cadavers.