骨密度随访不能改善骨折风险评估

《美国医学会杂志》(JAMA)9月24日在线发表的一项骨质疏松研究显示，在首次测定骨密度(BMD)后4年进行再次测定对于进一步改善骨折风险评估没有什么价值(JAMA 2013;310:1256-62)。

为了确定重复BMD检查是否有用，波士顿Hebrew SeniorLife老化研究所的Sarah D. Berry医生及其同事检查了基于人群的前瞻性Framingham骨质疏松研究中310例男性和492例女性的髋部骨折和主要骨质疏松性骨折的发生率。

患者在1987年至1999年平均74.8岁时进行股骨颈首次BMD检查。那时没有患者正在接受骨质疏松治疗。患者在平均3.7年(2.4~6.0年)后进行至少1次重复BMD检查。随后随访患者约12年或至其死亡。

随访期间，113例患者(14.1%)发生≥1次主要骨质疏松性骨折。有88髋、24脊柱、5肩和33前臂骨折。

首次和第二次BMD评估之间的BMD丢失与后续骨折相关。然而，此类丢失评估所提供的临床价值并不超过首次BMD检查提供的临床价值。第二次BMD检查导致少数患者被重新归入髋部或主要骨质疏松性骨折高危组。但尚不清楚这么少的被重新归类的患者是否可作为支持目前每隔2年进行重复BMD检查的做法的依据。

研究者作出结论，在首次BMD检查后4年重复进行BMD检查很少会改变基于髋部骨折风险评分做出的骨质疏松临床管理。风险评分改变最大的患者是那些基于首次BMD检查和临床特征已被归入高危组的患者。虽然一些专家建议缩短高危患者再次筛查的间隔时间，但该研究的研究者根据性别、年龄、BMI、体重减轻、T评分或骨折风险评分分层发现，BMD改变与骨折之间的关联无差异。

研究者表示，虽然得出上述研究结果，但我们需认识到对于被第二次BMD检查重新归类的少数骨折高危患者，检测BMD丢失是最重要的。再次检查将使医生为这些患者(甚至是≥75岁的患者)提供骨质疏松药物，以减少骨折风险。然而，对于首次检查显示骨量正常或仅轻微丢失的大部分患者，需进行进一步研究，以预测哪些患者可能会过渡至高危骨折组并因此从重复BMD检查中获益。

该研究的局限性在于几乎所有患者为白人。在其他人种和种族人群中，重复BMD检查的效用可能有所不同。

该研究获美国国立卫生研究院等机构支持。Berry医生声明无相关经济利益冲突。一名研究者与安进等多家药企存在联系。

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By: MARY ANN MOON, Clinical Endocrinology News Digital Network

Performing a second bone mineral density measurement 4 years after an initial measurement was "of little value" in refining the estimation of fracture risk in osteoporosis, according to a report published online Sept. 24 in JAMA.

The finding calls into question the current practice of performing serial bone mineral density (BMD) tests at even shorter 2-year intervals to enhance fracture risk assessment, the study investigators noted.

In a secondary analysis of data from the Framingham Osteoporosis Study, BMD change during a 4-year interval "provided little additional information beyond baseline BMD for the clinical management of osteoporosis," said Dr. Sarah D. Berry of the Institute for Aging Research, Hebrew SeniorLife, Boston, and her associates (JAMA 2013;310:1256-62).

The appropriate interval between BMD assessments remains controversial, and studies of the issue have yielded mixed results.

Studies that reported a strong association between BMD loss during a short interval and subsequent fractures typically focused on the small subgroup of patients who had accelerated bone deterioration. Other studies primarily involving patients with low or normal bone loss have reported only a weak association between BMD loss and later fractures, the investigators said.

To determine whether repeat BMD testing is useful, Dr. Berry and her colleagues examined the rate of hip and major osteoporotic fracture among 310 men and 492 women in the prospective, population-based Framingham cohort.

The study patients underwent an initial BMD test of the femoral neck in 1987-1999, at a mean age of 74.8 years. None was receiving treatment for osteoporosis at that time. The patients then had at least one repeat BMD test a mean of 3.7 years later (range, 2.4-6.0 years later). The study participants then were followed for approximately 12 years or until they died.

During follow-up, 113 study patients (14.1%) had one or more major osteoporotic fractures. There were 88 hip, 24 spine, 5 shoulder, and 33 forearm fractures.

BMD loss during the interval between the first and second BMD assessments was associated with subsequent fracture. However, assessment of such loss provided little clinical value beyond that of the initial BMD test.

"The second BMD measure resulted in a small proportion of individuals [being] reclassified as [at] high risk of hip or major osteoporotic fracture," Dr. Berry and her associates said. But it remains unclear whether such a small number of reclassifications justifies the current practice of performing repeat BMD tests every 2 years, they added.

"We conclude that repeating a BMD test after 4 years would rarely change the clinical management of osteoporosis based on risk scores of hip fracture," the researchers explained. "Individuals with the greatest changes in risk scores were those who would have already been classified at high risk based on [the initial] BMD and [their] clinical characteristics."

Although some experts suggest that short rescreening intervals are warranted in high-risk patients, "we found no difference in the association between BMD change and fracture when stratified by sex, age, BMI, weight loss, T score, or fracture risk score," the study authors noted.

"Despite our findings, we recognize that detecting BMD loss would have been paramount for the small numbers of individuals reclassified by a second BMD test who went on to experience a fracture," Dr. Berry and her colleagues said. For those patients, a repeat screening test would allow physicians to give osteoporosis medications and reduce fracture risk, even among patients 75 years or older.

However, for the clear majority of patients who show normal or only mild bone loss at an initial screening, further study is needed to predict which patients are likely to transition to high risk of fracture and would therefore benefit from repeat BMD testing.

The study was limited in that almost all the patients were white. The usefulness of repeated BMD screening might be different in other racial and ethnic populations, the investigators said.

The National Institutes of Health, the National Heart, Lung, and Blood Institute, and the Friends of Hebrew SeniorLife supported the study. Dr. Berry reported no relevant financial conflicts of interest; one of her associates reported ties to Amgen, Ammonett Pharma, Eli Lilly, Hologic, Merck Sharpe & Dohme, Novartis, and Roche.