Low-frequency acoustic sweep monitoring of bone integrity and osteoporosis.

We developed a noninvasive method to evaluate bone structural integrity. It is based on the measurement of the dynamic characteristics of the bone using sweeping sound excitation in the range of acoustic frequencies. The Quality Factor (a measure of material damping) has been used as an indicator of the tendency of the bone to fracture. Results of animal studies have supported this hypothesis since linear correlations were observed between bone density, quality factor, and impact strength. A vibration excitation in the form of an acoustic sweep signal is applied to a bone to measure the quality factor. Rat bones were tested, obtained from animals with osteoporosis age-dependent (tested in vitro) or ovariectomy-induced (tested in vivo), and compared with bones of healthy (control) rats. The change in damping was, on average, equal or greater to the change in density. Moreover, excellent correlation of the quality factor was obtained with bone fracture energy measured with an impact test. During a vibration cycle, the changing strain results in temperature changes due to the reciprocity of temperature and strain. Nonreversible conduction of heat due to the unequal temperature change results in entropy production that is enhanced due to the stress concentration about the voids associated with bone porosity. Damping is a measure of the production of entropy. Its measure, the quality factor, represents a potentially useful tool for monitoring bone integrity, which is deteriorating in diseases characterized by disruption of the trabecular architecture, such as osteoporosis. A computational model yielded results that are in good correlation with the experimental results.

An intact N terminus is required for the anabolic action of parathyroid hormone on adult female rats.

Intermittent administration of parathyroid hormone (PTH) peptides increases bone density in animal and human models of osteoporosis. In vitro studies have demonstrated that PTH analogs lacking the first two amino acids can stimulate cell proliferation in certain cell systems, whereas fragments with an intact N terminus can be antimitogenic. We have tested whether the truncated PTH(3-38) fragment may be a better "anabolic analog" than PTH(1-38) by monitoring bone density and biomechanical properties of the femur in 6-month-old ovariectomized (OVX) rats. Either PTH fragment was administered subcutaneously (8 micrograms/100 g of body weight) 5 days/week, for 4 weeks, starting 1 week after surgery. During the entire study, untreated OVX rats lost 12.1 +/- 4.4% of their initial bone density. PTH(1-38) reversed the initial bone loss, leading to complete restoration of presurgery values after 4 weeks of treatment. Conversely, administration of PTH(3-38) resulted in 13.2 +/- 5.8% bone loss, while continuous estrogen infusion (10 micrograms/kg/day) prevented bone loss but did not reverse it. Sham-operated animals also experienced significant bone loss in the vehicle and PTH(3-38)-treated groups (-4.5 +/- 6.7%, and -7.6 +/- 2.8%, respectively), whereas a significant gain in bone density (+4.4 +/- 5.6%) was observed in the rats treated with PTH(1-38). A bone quality factor (index of strain energy loss) and the impact strength (resistance to fracture) were 25% and 44% lower in femurs explanted from OVX animals treated with either vehicle or PTH(3-38), compared with sham-operated animals. On the contrary, no difference was observed between OVX and control animals after treatment with PTH(1-38), indicating a preservation of the capacity to withstand mechanical stress. Thus, PTH(1-38) counteracts estrogen-dependent loss of mineral density and bone biomechanical properties and increases bone density in estrogen-replete animals. An intact N terminus sequence is necessary for this anabolic action of PTH.

Bone quality factor analysis: a new noninvasive technique for the measurement of bone density and bone strength.

The sensitivity of bone mineral density (BMD) as a predictor of fracture risk is limited by the fact that this index does not take into account the geometrical and material characteristics of bone. In contrast, both BMD and bone architecture influence the quality factor (QF), the fraction of the inverse of the energy lost in one cycle of deformation. In this study we have compared the sensitivity of a QF analyzer and dual-energy X-ray absorptiometry (DXA) in detecting the changes induced by ovariectomy (OVX) on the QF, impact strength, and BMD of the femur of mature rats. QF and BMD were measured noninvasively before and 4 weeks after OVX or sham operation using a QF analyzer developed in our laboratory and a Hologic QDR 2000 bone densitometry, respectively. Impact strength was measured in excised femurs at the end of the study. The in vivo short-term precision (coefficient of variation) of the QF analyzer was 1.9%. BMD and QF measurements were highly correlated (r = 0.80,p <0.0001). At baseline, QF and BMD were similar in OVX and sham-operated rats. At 4 weeks, BMD was 14.7 + or - 0.9% lower than at baseline (p < 0.001) in OVX rats and 5.3 + or - 1.3% lower in sham-operated rats (p <0.05). QF decreased 36.0 + or - 2.8% (p <0.0001) in OVX and 10.6 + or - 3.6% in sham rats (p <0.01). As a result, at 4 weeks the difference between sham-operated and OVX rats was larger (p < 0.05) by QF than by BMD. Moreover, QF correlated better than BMD with impact strength and the difference in impact strength between sham and OVX mice was closer to that in QF than that in BMD. These data demonstrate that QF analysis is a precise technique that is more sensitive than DXA in detecting the changes in bone density and strength induced by OVX. QF analysis may represent a new, simple, and economic technique for predicting fracture risk.

Ipriflavone improves bone density and biomechanical properties of adult male rat bones.

To assess the potential impact of ipriflavone on the biomechanical properties and mineral composition of bone, we administered two doses (200 or 400 mg/kg bw) of the drug orally to adult male rats for 1 month. Bone biomechanics were evaluated by vibration damping, an index of strain energy loss, and impact strength (the amount of energy required to fracture after a single impact). At the higher dose, ipriflavone significantly decreased vibration damping of rat femurs by 23.0 +/- 9.8% compared with control, vehicle-treated animals, suggesting a higher capacity to withstand dynamic stress. This result was confirmed by the impact strength studies showing that a higher energy (49.6 +/- 21.3% above control) was required to fracture femurs of rat treated with 400 mg/kg bw ipriflavone. The high dose of ipriflavone increased bone mineral density, assessed by both volume displacement and ash analysis (4.2% and 2.5% above controls, respectively). The relative content of calcium, phosphorus, and magnesium in the ashes was not different among the treated and untreated groups, indicating that no gross abnormalities in mineral composition of bone occurred after ipriflavone administration. Similarly, there were no differences in serum calcium and magnesium levels between treated and control animals at the end of the study, whereas lower circulating phosphorus levels were detected in the latter. Ipriflavone treatment was not associated with significant changes in serum alkaline phosphatase nor type I collagen telopeptide levels, two markers of bone turnover. In summary, 1-month treatment with ipriflavone increased bone density and improved the biomechanical properties of adult rat male bones without altering mineral composition.(ABSTRACT TRUNCATED AT 250 WORDS)

Material damping for monitoring of density and strength of bones.

The aim of this work was a preliminary assessment of the feasibility of using in vivo measurements of mechanical properties of bones to detect mineral loss and further to relate them to the tendency of the bone to fracture in the case of loss of minerals, such as in osteoporosis. Previous studies of bone strength in vitro have demonstrated that the decrease in bone strength in both the spine and the femur has strong correlation with the mineral content (BMC) measured with bone densitometry. It was demonstrated that loss of mineral in the bone is accompanied by substantial change of the main mechanical properties, decrease of the Young's modulus, and increase of the damping factor. The change in those properties is one order of magnitude greater than the change in bone density. Moreover, increase of bone density, by way of training, resulted in decrease of the damping factor that also was substantially greater than the change in density. The tests showed clearly that the change in mechanical properties was much greater than the change in bone mass density. This offers an attractive new alternative to the detection of bone mass loss as it appears that the change of the bone mass is well correlated to the change in these mechanical properties. In particular, the change in the damping factor of the material was found to be much more substantial than the bone density change. Therefore, the damping mechanism offers the vehicle for a direct assessment of the bone tendency to fracture due to the loss of mass, as tendency to fracture and mass loss are known to be related.(ABSTRACT TRUNCATED AT 250 WORDS)

Monitoring of fracture healing by lateral and axial vibration analysis.

The ability to monitor the healing of bone fractures is crucially important in their treatment. The aim of the present study was to develop and validate an objective method for monitoring fracture healing based on bone vibrational response. An analytic model was formulated, with which the mechanical parameters at the fracture site could be studied in relation to both lateral and axial bone vibration. Non-uniformities in the stiffness of the bone at the fracture site can be detected since they produce shifting of the vibration and the phase spectrum and result in strong coupling between the lateral and axial vibration response spectra. The validity of the model was tested in experiments using fresh cadaver tibiae with transverse osteotomy and materials simulating fracture callus. The results of the study of vibration amplitude and phase angle and the coupling of axial and lateral vibration in these experiments confirm our analytic projection. Preliminary results of in vivo investigations using the described method are encouraging.