What’s the Claim?
A secondary analysis of a large randomized trial conducted mostly in older patients in Australia found an association between increased levels of high-density lipoprotein (HDL) cholesterol and fractures, as well as fractures caused by minimal trauma (such as falls from a standing height). For patients whose HDL cholesterol was in the highest quintile (the mean HDL in this group was 89 ± 15 mg/dL), the increased fracture risk was about 33%.
How’s It Stack Up?
While most orthopaedic surgeons — even those who treat fractures every day — may be unaware of this issue, it’s a pretty hot topic among those who look for risk factors in large, epidemiologic studies. A commentary published alongside this study doubted whether HDL cholesterol causes the finding in question, and felt that residual confounding could diminish the utility of HDL cholesterol even as a biomarker or screening tool in this setting. We agree on the former point — authors of this sort of observational research (and a secondary analysis of a randomized trial counts as observational research) need to be very cautious about inferring cause/effect relationships. However, it looks to us that on the latter point, the JAMA Cardiology commentator was perhaps too severe. The authors did a nice job confirming their findings, which held up in sensitivity analyses that included only minimal trauma fractures, participants not taking medications for osteoporosis, patients who never smoked and reported that they did not drink alcohol, and participants who walked outside for less than 30 minutes per day and did not engage in any moderate or vigorous physical activity. In fact, another large study reported the same main finding about HDL’s association with fracture risk, which tends to give us confidence, though the shape of the association was somewhat different between the two studies. The differences in the details likely arise from differences in the study populations; the study we’re covering here included patients whose average age was 75 and who likely were of White race, while the comparator study we’re mentioning had more Black patients, who in aggregate were a few years younger.
What’s Our Take?
Rather than quibble over those details — and given that orthopaedic surgeons will likely treat neither the high cholesterol nor the osteoporosis, if present — we’re sharing this paper from a nonsurgical journal for a simple, practical reason: When going over your patients’ lab values, if you see an HDL cholesterol in the 80 mg/dL level or so, consider doing your part to “own the bone” and tip off the patient’s family physician. That individual can ascertain whether further imaging, such as DEXA scanning, is indicated. It’s your chance to do your good deed for the day, perhaps prevent a severe fracture, and maybe even save a life. Not a bad result for, as they say in old detective movies, “dropping a dime” and making a phone call.
Hussain SM, Ebeling PR, Barker AL, Beilin LJ, Tonkin AM, McNeil JJ. Association of Plasma High-Density Lipoprotein Cholesterol Level With Risk of Fractures in Healthy Older Adults. JAMA Cardiol. 2023;8:268-272.
Wilkins J, Rohatgi A. Higher High-Density Lipoprotein Cholesterol-Good Omen, Bad Omen, or Not an Omen at All. JAMA Cardiol. 2023;8:273-274.