Obesity, bariatric surgery and bone health: Still much to learn

Obesity and osteoporosis are growing health concerns worldwide. Their interrelationship is of interest given that adipocytes and osteoblasts are both derived from pluripotent stromal cells. Factors favoring differentiation toward one lineage (for example, fat) could be predicted to have detrimental effects on tissues dependent on the other lineage (for example, bone).

Kurt A. Kennel, M.D., of the Division of Endocrinology, Diabetes, Metabolism, and Nutrition at Mayo Clinic in Rochester, Minn., says: "Many endocrinologists first became aware of this relationship with reports of bone loss and fractures in patients with diabetes treated with rosiglitazone (Avandia), which increases adipocyte and decreases osteoblast genesis. While a low body weight has long been associated with an increased risk of fractures, obesity was historically felt to be protective against fractures. This notion was based primarily on the observation that obese individuals have higher bone density than do their lean counterparts.

"However, recent investigations reveal an increase in fracture risk at the ankle and humerus in women but not men with increased body mass index (BMI). Beyond BMI, body composition appears to matter, with greater degrees of visceral fat increasing, and lean body mass reducing, fracture risk in similarly obese subjects. Related, and of emerging interest, is the influence of marrow fat given its proximity to the bone microenvironment."

How can this paradox of more bone but more fractures be explained? L. Joseph Melton III, M.D., of the Division of Epidemiology at Mayo Clinic in Rochester, Minn., answers: "One theory stems from the observation that increases in bone strength among obese individuals, as measured by high-resolution images evaluated with finite element analysis, are not proportional to the excess weight. This could lead to relative bone fragility compared with normal weight individuals.

"Also, for some fracture types (for example, the ankle and humerus fractures noted by Dr. Kennel), increased rates of falling in obesity and higher loads at impact may play a role. In contrast, there is a lower risk of hip fractures in obese subjects, which can be explained in part by the biomechanical role that adipose tissue over the hip plays in absorbing impact energy in a fall."

Dr. Kennel adds: "Morbid obesity is increasingly being treated with bariatric surgery, and derangements of mineral metabolism leading to secondary hyperparathyroidism, bone loss and osteomalacia have long been observed after bariatric surgery. However, the fact that bone loss can occur even when mineral metabolism is optimized, and that it also follows medical weight loss, suggests that changes in neurohormonal, mechanical, nutritional and other factors must be involved.

"The fact that the higher levels of serum estrogens in obese men and postmenopausal women decline with weight loss is notable given the key role that sex hormones play in bone metabolism. Any weight loss, and especially surgical weight loss, is also associated with loss of skeletal muscle. That high protein intake and physical activity applied to a restricted energy diet preserved bone mass during weight loss relative to an equivalent energy restriction diet alone suggests that some of the factors favoring bone loss due to weight loss are modifiable."

Dr. Melton notes: "Ultimately, the occurrence of fractures out of proportion to expectations is the strongest evidence of a clinically important relationship. We recently reported an increase in the incidence of fractures among Olmsted County residents undergoing bariatric surgery at Mayo Clinic compared with that expected for community residents of like age and sex generally. A strength of our study was that it was population-based with a long duration of follow-up, noting that the average time to first fracture was about five years following surgery.

"In contrast, a study from the U.K. found no increased incidence of fractures after bariatric surgery compared with BMI-matched nonoperated subjects, but this finding was limited by an average follow-up of just over two years. Another key difference between these studies was the choice of bariatric procedure: The majority of subjects in the U.K. study underwent laparoscopic adjustable gastric banding, a less aggressive surgical procedure resulting in less weight loss, and possibly less detrimental to bone, than the gastric bypass procedures currently favored in the U.S.

"Because there are many unanswered questions and few prospective or intervention trials, there are no uniform guidelines for including obesity as a unique risk factor for fracture or for applying osteoporosis guidelines differently to obese or post-bariatric surgery patients. Until such information becomes available, clinicians should be equally vigilant in applying current osteoporosis prevention and treatment guidelines to obese and nonobese patients, as well as to those who have undergone a bariatric surgery."