Our data show that PTH can increase biochemical indicators of bone formation in the presence of pretreatment with the potent bisphosphonate, alendronate. This agrees with the majority of data generated in the rodent model of osteoporosis 12–14 but is distinct from data in the aged ewe 15 and a recent investigation using a PTH analog with preceding and ongoing alendronate therapy in the rodent. 16 These differences highlight the fact that animal models may not always be representative of human processes. Our pilot study indicates that in humans, the anabolic effect of daily subcutaneous PTH should not be abolished by alendronate. The combination of PTH and alendronate, therefore, remains a valid approach to the treatment of osteoporosis.
Osteoporosis is marked by a decrease in bone mineral density and an increased susceptibility to fracture. This disease affects millions of people each year, and several drugs are currently under review for use in patients already exhibiting severe symptoms. Intermittent administration of parathyroid hormone (PTH) has been shown to reverse bone deterioration. PTH is known to increase bone growth, most likely through an increase in hematopoietic cells. During the summer of 2008, I performed research at the University of Michigan School of Dentistry, in the Periodontics and Oral Medicine research laboratory, headed by Dr. Laurie McCauley. We studied the anabolic effects of parathyroid hormone (PTH) on bone growth, as well as the metabolic pathways that induce increased bone density and mass. Two separate projects were performed to investigate PTH-mediated bone growth, one in vivo and one in vitro. The in vivo study included histomorphometric analysis of vertebrae and tibia from hematopoietic deficient mice either treated with PTH (50µg/kg) or vehicle. These mice lack stem cell factor (SCF) and were of particular interest due to the role of SCF in bone growth. These studies were performed to determine if SCF present on osteoblast cells regulates the anabolic effect of PTH through binding to hematopoietic stem cells. The in vitro study included flow cytometric analysis of bone marrow cells from wild-type mice treated with PTH (50µg/kg) or vehicle. This was performed to determine how PTH increases hematopoietic cell number, whether by anti-apoptosis or increased cell proliferation.
The serum magnesium is not reflective of total magnesium stores. Unfortunately there is not a good test for magnesium, but a red cell Mg level is preferable to serum magnesium. Approximately 2/3 to ¾ of magnesium in blood is not attached to protein. In other words, approximately one-third is bound to protein, the rest exists as free occurs in the serum as approximately a 5:1 ratio to total serum calcium. Low magnesium is much more common than excess. Magnesium plays a role in both carbohydrate and protein metabolism and can be lost through the gastrointestinal tract, kidneys, and in sweat.