Bone turnover in age-related osteoporosis: early contributions of Pierre Delmas

Abstract

One cold evening in March, 1981, I arrived at the Rochester, MN Airport to meet a new postdoctoral research fellow from Lyon, France who had come to work for 6 months in my laboratory at the Mayo Clinic. Professor Pierre Meunier of the Claude Bernard University had recruited this promising young physician to his group and had sent him to be exposed to the American approach to clinical investigation. This was my introduction to Pierre Delmas. From the beginning, it was clear that he was special. Although the original plan was for him only to observe, Pierre wanted his own research project. Indeed, he wanted multiple research projects and not just minor ones at that. When I pointed out that this was unrealistic given his limited time in Rochester, he replied, “Give me a chance; I'm a hard worker.” And so he was. An important challenge in bone research at that time was the development and application of new biochemical markers for assessing bone turnover. Available markers were crude and imprecise, and bone histomorphometry was invasive and had other limitations. The groups at Children's Hospital in Boston and at the University of California at San Diego had recently developed sensitive assays for osteocalcin, a newly discovered Gla-containing, bonerelated protein. After secretion by osteoblasts, a fraction of the osteocalcin back diffuses into the circulation. Thus, the assay of serum osteocalcin held great potential as a sensitive and specific marker for bone formation. I suggested to Pierre that he attempt to develop an inhouse assay for this new marker which could subsequently be used for studies in osteoporosis. My colleague, Dr. Kenneth G. Mann, an authority on Gla-containing coagulation proteins, agreed to supervise this effort. Pierre rapidly isolated the osteocalcin-containing fraction from human bone samples and, in less than 3 months, had obtained high antibody titers against it in immunized rabbits. With the new osteocalcin immunoassay in hand, he negotiated a 12-month extension of his time in Rochester to apply it. During this interval, he completed and published five papers. In the early 1980s, a crucial unresolved issue was the characteristics of bone turnover in postmenopausal and senile osteoporosis. At that time, the field still was heavily influenced by the 1940s Albright dictum that postmenopausal osteoporosis was caused by decreased bone formation associated with normal bone resorption. Indeed, most prior studies had found that overall bone turnover was not increased. Radiocalcium kinetic studies found that the bone formation rate in osteoporosis was within the normal range. Several bone histology studies had found varying results in women with postmenopausal osteoporosis, although most showed a decrease in bone formation. Results from histological measurements of bone resorption were conflicting. Moreover, any increase in eroded surfaces could have resulted from either increased resorption or from their decreased removal due to impaired bone remodeling. However, the Meunier group had demonstrated histological heterogeneity using tetracycline-based histomorphometry of iliac biopsy samples in a large group of osteoporotic women (mean age of 65 years). Although they found that overall mineral apposition rate was significantly decreased, 10% of the osteoporotic subjects had increased values [1]. For senile osteoporosis, the evidence implicating Osteoporos Int (2009) 20:1289–1290 DOI 10.1007/s00198-009-0995-x