Pierre D Delmas 1950—2008 (2008)

The bone and mineral community lost one of its most illustrious members when Pierre Delmas died on July 23, 2008 at the pinnacle of a long and productive career as an investigator, leader, and mentor. Pierre was Professor of Medicine, Claude Bernard University; Chairman of the Department of Rheumatology, Edouard Herriot Hospital; and Director, INSERM Research Unit 403 “Pathophysiology of Osteoporosis,” Edouard Herriot Hospital, Lyon, France. He received his medical degree and specialty training in rheumatology at the Claude Bernard University and developed his interest in bone biology under the mentorship of Pierre Meunier, with whom he studied the effect of clodronate on bone turnover. He continued his training as a postdoctoral research fellow in the laboratories of Larry Riggs and Ken Mann at the Mayo Clinic where he worked on the pathophysiology of osteoporosis, the biochemistry of bone matrix proteins, and the development of serum assays for them as indices of bone turnover. On returning to France, he built on these early studies and soon achieved international recognition as one of the leading researcher in our field. Pierre's contributions to the study of osteoporosis and metabolic bone diseases have been recognized by his peers and were acknowledged by many honors including the Andre Lichtwitz Prize (1985); the Prix de Fondation Nationale de la Recherche Medicale (1985); the Philippe Bordier Prize (1985); the Fredric C. Bartter Award for excellence in clinical investigation from the American Society of Bone and Mineral Research (2004); and the Medal of Honor from the International Osteoporosis Foundation (2006). He was President of the Board of the European Foundation for Osteoporosis (1996–1998), President of the International Osteoporosis Foundation (1998–2008), and Chair of the Health Council on Osteoporosis. He was also Associate Editor of Bone, Co-Editor of Osteoporosis International, and a member of the editorial boards of virtually every major journal in our field. Pierre Delmas was a colossus among clinical investigators in our field. He published >400 full-length papers that are remarkable, not only for their large numbers and quality, but also for their breath and depth, spanning many aspects of metabolic bone diseases. His group was accorded the number 1 worldwide ranking in the ISI survey of publications on osteoporosis based on citations per paper. Also, based on the number of citations, the ISI ranked Delmas among the top 100 French authors in any of the 22 surveyed branches of science. He is perhaps best known for his studies with measurement of biochemical markers of bone turnover. Indeed, the current central role of bone markers in research and in the clinical assessment of osteoporosis and other metabolic bone disease are testaments to the importance of his work. In a series of studies, he showed that biochemical markers in serum and urine were predictors of bone loss, fracture risk, and the efficacy of treatment. More recently, he developed, validated, and used a series of markers assessing the severity of joint diseases, including the first specific marker for synovial metabolism in vivo, showing that it was elevated in both rheumatoid arthritis and osteoarthritis and was a predictor of joint destruction in rheumatoid patients. He also developed and characterized type II collagen C-telopeptide and the N-propeptide of type II collagen as markers for cartilage destruction in osteoarthritis. He further showed that bisphosphonates decreased the excretion of type II collagen breakdown, suggesting that it was a useful marker in osteoarthritis for quantifying its activity and monitoring treatment. He made extensive contributions to research on the epidemiology of fractures and osteoporosis, the diagnosis and pathophysiology of postmenopausal osteoporosis, osteoporosis in men, and steroid-induced osteoporosis. He was the first to show using bone markers that the main cause of bone loss in postmenopausal osteoporosis was an absolute increase in bone resorption, although there was a great deal of histological heterogeneity among patients with a spectrum of high, normal, or low remodeling. He emphasized the importance of the vigorous remodeling taking place on the endocortical surface of bone, more active than on trabecular surfaces, and the importance of declining periosteal apposition in the face of increasing endocortical resorption. This observation dispelled the notion of a compensatory increase in formation on the periosteum in the face increasing resorption on the endocortical surface. He was the first to show that bone turnover increased with aging, rather than decreased as was formerly believed, and that bone turnover markers with aging correlated with increases in age-related increases in serum PTH, findings that resulted in a sea of change in thinking about the pathogenesis of age-related osteoporosis. In other studies, he dispelled the notion that polymorphisms of genes coding for the vitamin D receptor, COL1A1 Sp1 binding site, and IL-6 were major causal factors in bone loss by showing that they were not associated with BMD and bone turnover. He characterized changes in bone mass and bone turnover with aging in men and was among the first to show that decreases in serum bioavailable estradiol was a major determinant of their bone loss in men. He also showed that physical training did not reverse the inhibition of osteoblast function induced by high-dose prednisone. He was Principal Investigator of the celebrated OFELY and EPIDOS epidemiology studies in postmenopausal and elderly women, respectively, which have contributed enormously to our understanding of the historical, biochemical, genetic, and other risk factors for bone loss and fractures. He developed lateral dual photon absorptiometry of the lumbar spine and showed that it could eliminate artifacts caused by spinal osteoarthritis. More recently, he and his collaborators have published pioneering research on bone microstructure in osteoporosis assessed by high-resolution pQCT and have also evaluated the effects of bone size and shape in determining bone strength and predicting fracture risk. Few if any clinical investigators have done more to evaluate the efficacy of new drugs for osteoporosis treatment. He participated in the design, execution, and publication of most of the major drugs now used to treat osteoporosis including alendronate, risedronate, raloxifene, ibandronate, and zoledronic acid. In early studies, he assessed the therapeutic efficacy of sodium fluoride, calcium and vitamin D, and estrogen. In a miscellany of other studies, he showed that there was dense nervous innervation of bone tissue, that osteoclasts had functional glutamate receptors, and that antagonists of NMDA Glu receptors impaired osteoclast sealing zone formation and resorption activity. He showed that low bone formation was a feature of both the hypercalcemia of malignancy and bone metastasis and that it forecast a poor prognosis in multiple myeloma. In a murine model of prostate and breast cancer, he showed that bisphosphonate treatment inhibited the development of adhesions between the cancer cells and bone surfaces and that this reduced the malignant invasion of the unaffected bone. He has also related biochemical markers to bone pathology and histomorphometry in Paget's disease and in assessing responses to bisphosphonates. Pierre was also a gifted mentor. He supervised the research programs of 24 students for MS degrees, 30 students for MD or PhD degrees, and 16 postdoctoral research fellows. He believed in his students and helped them develop independence and make their own contributions. On receiving the Bartter Clinical Investigation Award at the 2004 ASBMR Annual Meeting, he summed up the message that he tries to impart to his students and trainees as, “Why choose a career in biomedical research? It is not because it may lead to jobs, promotions, or honors, although it may. Rather, it is because research is fun. It is more fun than anything else that you can do.” Perhaps no one has done as much in the worldwide struggle against osteoporosis as has Pierre Delmas. His vision was for a global organization in which all member societies had an equal voice and worked in unison toward the common goal of controlling osteoporosis. This vision led to the creation in 1998 of the International Osteoporosis Foundation (IOF) from a merger of the European Foundation for Osteoporosis and the International Federation of Societies for Skeletal Disease. Subsequently, the National Osteoporosis Foundation of the United States was brought into an alliance with the IOF as a member of the Committee of National Societies. The IOF now comprises a worldwide network of 183 member societies in 89 locations dedicated to improving the diagnosis, prevention, and treatment of osteoporosis and to educating caregivers and the laity about the disease. He continued to nurture these fledgling societies throughout the world by his participation (25 times or more per year) in their local activities and educational programs. Also, through his leadership, numerous programs for osteoporosis prevention and management were created in areas of the world where information about osteoporosis was previously unavailable. Global awareness of osteoporosis was fostered through regional training courses, founding of a quarterly journal (Progress in Osteoporosis), and by establishing World Osteoporosis Day. He will be remembered for his research and many academic achievements but, most of all, he will be remembered because he was Pierre— a man full of curiosity, excitement, and joie de vivre. He had great presence, charm, and style and was a natural leader and loyal friend. Despite his illness, he maintained his humor and his interest in the work of others, and he continued to direct his research program and to write and review manuscripts. His passing leaves a deep and abiding void in the lives of his many friends and colleagues. We can find solace in the wonderful memories that he has left for us, although at international meetings we will never again hear the voice at the microphone with those incisive questions that invariably began with “. . . Delmas, Lyon, France.” He is survived by his devoted wife, Debra, who he met, wooed, and won during his fellowship in the United States, and by his two talented children, Gauthier and Olivia.