New promising avenue for the simvastatin combination with residronate,strontium ranelate and raloxifene in experimentally-induced osteoporosis

Aim of the workThis is the first experimental study to assess the possible synergistic effects of simvastatin combination with residronate, strontium ranelate and raloxifene on glucocorticoid induced osteoporosis (GIO) in female albino rats.Materials and methods48 mature healthy female albino rats were randomly allocated into 6 main groups (8 rats /group) and received all drugs daily orally for 6 weeks. (G1) negative control group; (G2) osteoporotic group that received prednisolone at 15 mg/kg/day; (G3) prednisolone + 10 mg/kg/day simvastatin; (G4) received prednisolone + simvastatin + residronate 1 mg/kg/day; (G5) prednisolone + simvastatin + strontium ranelate 600 mg/kg/day; (G6) prednisolone + simvastatin + raloxifene at 1.25 mg/kg/day. After 6 weeks, mean arterial blood pressure (MAP), ejection fraction and left ventricular diameter were assessed. Bone histomorphometry, serum level of bone specific alkaline phosphatase (BsALP), osteocalcin (OCN), calcium, phosphorus, AST and ALT and bone mineral assessment by DEXA.ResultsSimvastatin combined regimens-treated groups exerted significant marked amelioration of osteoporotic changes by achieving the highest histopathological score, bone mineral density by DEXA scan, increase in serum Ca, OCN and decrease in BsALP especially in simvastatin combined groups (G4 and G5) whereas, simvastatin combined groups (G4 and G6) exerted more significant improvement in cardiovascular adverse events regarding the elevated MAP, cardiac hypertrophy and dysfunction as compared to osteoporotic non-treated group2 (p < 0.0001).ConclusionSimvastatin combined regimens have promising synergistic effects on bone microarchitecture with cardiovascular protective effects which might be considered by clinicians as valid preventive and therapeutic strategy in patients with osteoporosis with or highly susceptible to cardiovascular disease.     

Osteonecrosis of the jaw related to everolimus: a case report

Antiresorptive agent-related osteonecrosis of the jaw results in appreciable morbidity in affected patients. Nowadays many physicians prescribe an antiangiogenic agent for the management of malignant metastases. Everolimus is a serine–threonine kinase that acts as an inhibitor of mammalian target of rapamycin, which results in reduced growth of cells, angiogenesis, and survival of cells. We report the first case to our knowledge of osteonecrosis of the jaw that seemed to result from the additive effect of everolimus.     

Treatment of pathologic fractures of the mandible in stage III medication-related osteonecrosis of the jaw—an observational study

Purpose

The treatment of pathologic fractures in stage III medication-related osteonecrosis of the jaw (MRONJ) remains challenging. The treatment in the literature is controversial, varying from extensive and aggressive surgery with resections and musculocutaneous free flap reconstruction to conservative treatment with only mouth rinses and/or antimicrobial treatment. The purpose of this study was to analyse the results of the treatment protocol in the Leiden University Medical Center in the Netherlands.

The increase in spinal bone density that occurs in response to fluoride therapy for osteoporosis is not maintained after the therapy is discontinued

In 44 osteoporotic subjects who had been treated with fluoride for 37±16 months, the fluoride was discontinued because they had shown fluoride-dependent increases in trabecular spinal bone densities from low initial levels (below the fracture threshold) to values that were equivalent to normal peak bone densities in the spines of young adults. During the subsequent period, after discontinuation of the fluoride therapy (i.e. 19±9 months), spinal bone density decreased in 73% of the subjects (i.e. 32 of 44,p<0.03), at a rate that was comparable to the rate of the previous gain that had occurred during the treatment with fluoride (i.e. –3.23±2.39 mg/cm³ per month, compared with +3.91±1.96 mg/cm³ per month in this subgroup of patients,p<0.001). Although 9 of the 44 subjects showed continuing increases in spinal bone density after discontinuation of the fluoride therapy, spinal bone density decreased in the entire group of 44 at an average rate of –1.02±4.72 mg/cm³ per month (p<0.001, compared with the rate of the previous gain during the treatment with fluoride; i.e. +3.83±1.82 mg/cm³ per month). Surprisingly, our data showed that the rate of decrease in spinal bone density during the post-fluoride period was not affected by concurrent (undesigned) treatment with calcium, calcium plus estrogen, or calcium plus calcitriol. The cessation of fluoride therapy was also associated with a decrease in serum alkaline phosphatase activity (i.e. a decrease from the elevated levels that were observed during the period of fluoride therapy, back to the original, pre-treatment levels;p<0.001), and that the rate of spinal bone loss after cessation of fluoride could be correlated with the prior rate of increase in serum alkaline phosphatase activity that had occurred during the treatment with fluoride (n=44,r=0.312,p=0.039). Together, the observations from this retrospective analysis of data obtained from our clinical subjects suggest that fluoride-treated osteoporotic subjects who have exhibited increases in trabecular spinal bone density are at risk for bone loss after discontinuation of the fluoride therapy.     

Femoral shaft strains during daily activities: Implications for atypical femoral fractures

Background

Atypical femoral fractures are low-energy fractures initiating in the lateral femoral shaft. We hypothesized that atypical femoral fracture onset is associated with daily femoral strain patterns. We examined femoral shaft strains during daily activities.

Methods

We analyzed earlier calculations of femoral strain during walking, sitting and rising from a chair, stair ascent, stair descent, stepping up, and squatting based on anatomically consistent musculoskeletal and finite-element models from a single donor and motion recordings from a body-matched volunteer. Femoral strains in the femoral shaft were extracted for the different activities and compared. The dependency between femoral strains in the lateral shaft and kinetic parameters was studied using multi-parametric linear regression analysis.

Findings

Tensile strain in the lateral femoral shaft varied from 327 με (squatting) to 2004 με (walking). Walking and stair descent imposed tensile loading on the lateral shaft, whereas the other activities mainly imposed tensile loads on the anterior shaft. The multi-parametric linear regression showed a moderately strong correlation between tensile strains in the lateral shaft and the motion kinetic (joint moments and ground reaction force) in the proximal (R² = 0.60) and the distal shaft (R² = 0.46).

Interpretation

Bone regions subjected to tensile strains are associated with atypical femoral fractures. Walking is the daily activity that induces the highest tensile strain in the lateral femoral shaft. The kinetics of motion explains 46%–50% of the tensile strain variation in the lateral shaft, whereas the unexplained part is likely to be attributed to the way joint moments are decomposed into muscle forces.