NASHVILLE, Tenn. – When evaluating patients with metabolic bone disease, DXA is a safe, accurate and precise tool that correlates positively with fracture risk. However, it does not always give a complete representation of what is going on with the patient.
According to a presenter at the 24th annual American Association of Clinical Endocrinologists Scientific & Clinical Congress, utilizing HRpQCT, or extreme CT, and incorporating trabecular bone score information or microindentation analysis could provide additional insight into diagnosing fracture risk for patients with conditions like primary hyperparathyroidism or type 2 diabetes, whose risk would not be apparent with DXA analysis alone.
There are several clinical problems when looking at metabolic bone diseases that can possibly be solved by looking beyond DXA measurements, said John Paul Bilezikian, MD, MACE, chief of the division of endocrinology and director of the metabolic bone diseases unit at the College of Physicians and Surgeons at Columbia University, NY.
John Paul Bilezikian
Speaking during a conference presentation titled “Microarchitecture of Bone and its Clinical Relevance,” Bilezikian told Endocrine Today that “there is a new frontier of diagnostic evaluation of subjects who have metabolic bone disease, and this frontier is taking advantage of new technologies that are helping to explain issues of fracture risk in certain diseases – like hyperparathyroidism, diabetes, and the [plate-to-rod] ratio difference – that we cannot explain by the usual bone density test and the usual FRAX score. Down the road, hopefully, these technologies are going to become more available so the practitioner can have a much better database by which to make decisions about who should be treated for bone loss.”
A sense of false security
Multiple studies have shown that there is an increased risk of fracture in patients with both primary hyperparathyroidism and type 2 diabetes, Bilezikian said, yet DXA analysis for these patients will often provide a T-score that puts patients in a low-risk category.
Often in patients with type 2 diabetes, bone mineral density is higher, Bilezikian said.
“So based upon DXA, we should expect that fracture risk in diabetes is lower than age- and weight-matched controls,” Bilezikian said. “That expectation has not been borne out. In fact, fracture risk is higher [in these patients].”
FRAX, Bilezikian said, does not take into account important factors like bone turnover, rate of bone loss, secondary causes besides rheumatoid arthritis, and long-term risk and fall risk.
“So, we have the need to learn more,” Bilezikian said. “We know that DXA is helpful ... but there are situations where neither DXA nor FRAX gives us the information we need.”
While HRpQCT technology is still not readily available everywhere, the imaging is safe and precise, Bilezikian said, and it offers clinicians the opportunity to take analysis a step further.
“One can go further with this imaging – take the image by HRQpCT and resolve the trabecular arch into topologically horizontal or vertical plates,” Bilezikian said. “By looking at the [plate-to-rod] ratio … one can gain some measure of bone strength.”
Trabecular bone score, Bilezikian said, takes advantage of this idea. Combining FRAX with trabecular bone score provides more information than using data from either alone, he said.
“There is strong evidence that trabecular bone score predicts strong fracture risk independent of DXA and FRAX,” Bilezikian said. “Trabecular bone score can enhance fracture prediction from FRAX.”
Microindentation technology can also be helpful, Bilezikian said, though more studies are needed before there is a strong sense of how to best evaluate the skeletons of patients with type 2 diabetes.
Impact of genetics
Bilezikian presented another “clinical puzzle” that DXA or FRAX alone cannot solve -- why in study after study, Chinese women show a lower risk of fracture despite having a lower bone mineral density according to DXA measurements.
“Asians have lower bone mineral density by DXA than other racial groups,” Bilezikian said. “This should put them at higher risk … but in fact, they are not at higher risk. So, one possibility is DXA-based bone density is giving us a falsely lower value, because DXA … is influenced by bone size.
“Suppose you have a Chinese woman who has a bone density test that is low,” Bilezikian said after the presentation. “And if you don’t know that there is a difference in fracture risk based on a woman with a Chinese ancestry, you might be tempted to treat that woman, when her fracture risk isn’t that high.”
“Studies of premenopausal Chinese women have revealed smaller bone size, but greater cortical and trabecular thickness vs. white women,” Bilezikian said, meaning other forms of analysis are needed to properly evaluate their fracture risk.
“There’s an 85-fold greater chance of finding a Chinese person in the top quartile [for fracture] than a Caucasian person,” Bilezikian said. “It’s amazing. That says there is a gene.
“I think these technologies are becoming more useful … in the assessment of our patients,” Bilezikian said. “Moreover, they’re giving us information about fracture risk that goes beyond DXA and FRAX.” – by Regina Schaffer
Bilezikian JP. Oral presentation TGS3. Presented at: AACE 24th Annual Scientific & Clinical Congress; May 13-17, 2014; Nashville, Tenn.
Disclosure: Bilezikian reports financial ties with Amgen, Merck & Co., NPS Pharmaceuticals and Radius Health.