Boston—June 6, 2011
The study demonstrated that maintaining a circulating vitamin D level above 33 ng/ml is associated with a seven-fold greater likelihood of having a more favorable outcome with bisphosphonate therapy. Last November, the IOM issued recommendations that 25-Hydroxy vitamin D levels of 20-30 ng/ml were adequate for normal, healthy people.
“You are seven times more likely to respond to bisphosphonates if your 25-Hydroxy vitamin D level is 33 ng/ml and above. If you want to see a particular outcome from this treatment, then maybe 20 to 30 is not appropriate,” said Richard Bockman, M.D., Ph.D., chief of the Endocrine Service at Hospital for Special Surgery, who directed the study. “When you see a seven times greater effect, that is pretty impressive.”
More than 20 million people take bisphosphonates to preserve and improve skeletal health, and reduce the risk of fractures that can be caused by low BMD and osteoporosis. These drugs, however, do not work well in some patients. Because vitamin D is important to bone health, the researchers investigated whether they could identify levels of vitamin D that are associated with improved outcomes in patients taking bisphosphonates.
They conducted a retrospective chart review of patients seen in an osteoporosis practice of Hospital for Special Surgery. They identified subjects who were female, postmenopausal, had been taking one of four FDA-approved bisphosphonate drugs for at least 18 months, and had undergone at least two BMD scans separated by 18 to 60 months. The four drugs are alendronate, residronate, ibandronate and zolendronate. Patients were not included if they were nonadherent to bisphosphonate therapy, were chronic steroid users, or had metabolic bone disease or chronic kidney disease.
The researchers collected data on age, body mass index, type of bisphosphonate taken, treatment duration, concurrent calcium supplementation, fracture prior to and during bisphosphonate therapy, BMD and T-score at four sites—lumbar spine, femoral neck, trochanter, and total hip—from the two most recent bone scans. “The way the data are expressed for a bone density is how many standard deviations are you away from the normal,” explained Dr. Bockman. “One standard deviation from the normal is a T score of one. Two standard deviations is a T score of two. Below the normal, it is a minus two and above the normal is a plus two. If your bone density is more than 2.5 standard deviations below the normal, that defines a low bone mass that is considered to be osteoporosis.” The researchers also collected data on circulating levels of vitamin D, obtained with and between the two most recent bone scans.
Patients were deemed nonresponders if they had more than a 3 percent decrease in BMD between the initial and follow-up bone scans, a low-trauma fracture or a T-score less than -3.0 despite at least 24 months of bisphosphonate therapy.
The study included 160 patients, of whom 89 were responders, and 71 were nonresponders, with 42 having decreased BMD, 17 sustaining a fracture, and 12 having a persistent low T-score. The investigators found that only 16.8 percent of responders whereas 54.9 percent of nonresponders had vitamin D levels less than 33 ng/ml. Patients with an average circulating vitamin D level of 33 ng/ml and above had a seven-fold greater likelihood of having a favorable response to bisphosphonates. “We selected 33 as the cutoff and subsequently showed that it was the right choice, with more being better,” Dr. Bockman said. Nonresponse rates were higher in patients who had low levels of vitamin D: <20 ng/ml (83.3%), 20-30 ng/ml (77.8%), 30-40 ng/ml (42.3%), and >40 ng/ml (24.6%).
“If you look at the medical literature, researchers talk perhaps about a 20 percent increase in response rate, occasionally a doubling, but when you see a sevenfold improvement in outcome, you have to be impressed that it is probably important,” said Dr. Bockman, who is also professor of Medicine in the Endocrine Division of Weill Cornell Medical College.
Before this study, researchers had not formally studied the relationship between vitamin D levels and the effectiveness of bisphosphonates. “There has been a lot of controversy over the correct vitamin D level for people to have,” Dr. Bockman said. “Vitamin D status should be optimized to improve outcomes in patients taking bisphosphonates.”
Dr. Bockman pointed out that three associations—the American Geriatric Society, Endocrine Society, and the American College of Rheumatology—are coming out with or have guidelines that recommend vitamin D levels higher than the IOM recommended levels for healthy people.
Other investigators involved with the study include Albert Shieh, M.D., a third year medical resident, and Amanda Carmel, M.D., an instructor in Medicine, both at NewYork-Presbyterian Hospital/Weill Cornell Medical College. The study was supported by the Mary and David Hoar Fellowship of the New York Academy of Medicine to Dr. Amanda Carmel and by the National Institutes of Health funded Clinical and Translational Science Center of Weill Cornell Medical College and Hospital for Special Surgery.