Paradigm shift at the ASBMR

ASBMR 30th Annual Meeting

The American Society for Bone and Mineral Research held its 30th annual meeting in Montreal between September 12 and 16. About 5,000 people attended, including roughly equal numbers of clinicians and scientists. As in the Endocrine Society, a substantial fraction of the ASBMR members work in more than one area.

Featured sessions included the Gerald Auerbach Lecture, presented by Dr. Mina Bissell on “The Architectural Basis of Tissue Specificity: The Relationship Between the Genome and 3-D Structure,” and the Louis Avioli Lecture, presented by Dr. Clifford Rosen on “Bone Marrow Fat: Neighbor or Nemesis?” Featured symposia on vitamin D, skeletal oncology, stem cells, pediatric bone mass accrual, skeletal dysplasia, cancer and bone, emerging research and therapeutic strategies, SERMs and SARMS, and oxidative stress provided attendees with an opportunity to hear leading investigators summarize the cutting edge in each of these areas. Finally, a session on the history of the society gave newer members a chance to hear about the ASBMR’s early days from those who were there.

These sessions notwithstanding, I believe that the most important message that emerged from the meeting was not delivered at a definable moment. Rather, the message emerged as a constant background that permeated a majority of the basic and translational and a significant fraction of the clinical presentations. That message is that the bone community has now fully embraced Harold Frost’s mechanostat hypothesis, that states that bone modeling and remodeling is largely a response to mechanical loading applied to the skeleton. According to this model, mechanical loading is a physiological variable, like hormone levels, subject to feedback control exerted by the (re)modeling response of bone. Also, as in the case of other hormonal feedback loops, there is cross-talk between the mechanostat and other hormonal axes.

For many years, the mechanostat hypothesis was considered an elegant model without much in the way of experimental support, but the past several years have provided a wealth of information about the details by which bone senses and responds to mechanical loading. Importantly, the story has relied on truly translational investigations, in which both clinical and laboratory observations have been vital. The osteoporosis pseudoglioma syndrome and families with autosomal dominant high bone mass provided the key to understanding the centrality of Wnt signaling to the physiology of skeletal loading. Recent work on osteocyte biology has led to the beginning of understanding of the role of these cells and their canalicular network in integrating mechanical stimuli and translating them into changes of osteoblast and osteoclast activity.

Closer to the clinic, work is ongoing on developing passive vibration systems to apply anabolic stimuli to patients whose ability to perform weight bearing exercise is limited. Similar interventions are also being considered as a possible countermeasure for prolonged space missions. Components of the mechanotransduction loop are being assessed as targets for pharmacologic intervention. Load-stimulated modeling is also central to the emerging understanding of bone size, trabecular architecture and their relationship with bone mineral density.

The field has advanced dramatically during the 21st century. Bone biology and bone medicine is no longer about BMD and how it can be preserved in aging. It is about how the skeleton responds to mechanical, neural and endocrinological signals to cause the characteristic changes observed in the skeleton over the lifecycle and how these might be harnessed to prevent low trauma fractures. The era of integrative bone physiology has arrived, and clinical understanding will soon demand that practicing physicians keep pace.