Allison R. Altman, Wei-Ju Tseng, Chantal M.J. de Bakker, Beom Kang Huh, Abhishek Chandra, Ling Qin, X. Sherry Liu
Daily injections of parathyroid hormone (PTH) are the only FDA-approved anabolic treatment for osteoporosis; however PTH is only clinically approved for treatment periods of up to 24 months. To enhance its anabolic effect, combining PTH with anti-resorptive therapy was proposed and expected to maximize the effectiveness of PTH. The current study aimed to elucidate structural mechanisms through which combination therapy can further improve bone strength over a limited treatment window of 12 days, to more closely examine the early phase of the anabolic window. We examined 30 female rats treated with either vehicle (Veh), alendronate (ALN), PTH, or both PTH and ALN (PTH + ALN). Standard and individual trabecula segmentation (ITS)-based microstructural analyses were performed using in vivo micro-computed tomography. We found an increase in BV/TV in all treatments with the highest in the PTH + ALN group. Tb.Th* increased in both PTH and PTH + ALN groups well beyond that of the Veh or ALN group. SMI decreased in all treatments with PTH + ALN having the greatest tendency toward plate-like structures. ITS confirmed the trend toward more plate-like structures with increased plate Tb.N and increased plate-to-rod ratio that was most pronounced in the PTH + ALN group. Using image-based finite element analysis, we demonstrated that stiffness increased in all treatment groups, again with the largest increase in the PTH + ALN group, indicating the resulting structural implications of increased plate-like structure. Static and dynamic bone histomorphometry and a serum resorption marker confirmed that PTH + ALN significantly increased bone formation activities and suppressed bone resorption activities. Overall the results indicate that PTH + ALN treatment has an additive effect due to a preferential increase in plate-like structures.