手术对于减少副甲状腺机能亢进症之骨折效果最佳


  【24drs.com】一篇新发表的观察型研究指出,原发性副甲状腺机能亢进症之处置,采用从副甲状腺移除良性肿瘤的简单手术,可显著降低一段时间的骨折风险,而若以任何双磷酸盐类药物治疗相同患者,则会增加前述风险。
  
  第一作者、加州洛杉矶分校大卫格芬医学院内分泌外科主任Michael Yeh医师表示,这些患者10年期间的骨折机率约为5%,这是令人害怕的-因为比车祸还常见。
  
  他断言,虽然数年来我们相信,双磷酸盐类药物可用于治疗原发性副甲状腺机能亢进症引起的骨质疏松症,我们的证据显示,副甲状腺手术是唯一可以降低骨折风险的方法。
  
  这篇研究在线发表于4月4日内科医学志。
  
  Yeh医师等人解释,原发性副甲状腺机能亢进症是常见的内分泌疾病,在美国影响约1/400的女性与1/1200的男性。原发性副甲状腺机能亢进症若未治疗,会导致骨质密度(BMD)随著时间流失,引起发生骨质疏松与相关骨折风险增加的顾虑。
  
  他们使用Kaiser Permanente Southern California Laboratory Management System回溯检视在1995-2010年间,生化诊断有原发性副甲状腺机能亢进症的患者;原发性副甲状腺机能亢进症患者的传统定义是,血清总钙质数值>2.63 mmol/L(>10.5 mg/dL) 以及过高的副甲状腺素值(PTH):>65 ng/L。
  
  在2012年底针对总髋骨与腰椎测量BMD。整体而言,这篇研究纳入6,272名原发性副甲状腺机能亢进症患者,有36%在开始时有骨质减少,其中53%有骨质疏松。
  
  这些患者中,22%使用一种双磷酸盐类药物治疗,疗程中位数为55个月,其它22%进行了副甲状腺切除术,其余55%则是仅有维持观察。
  
  中位数4.5年的追踪期间,研究者确认940例骨折,其中178例是髋骨骨折,762例是髋骨之外的其它部位骨折。
  
  Yeh医师等人报告指出,在各个时间点,副甲状腺切除术都与骨折风险降低有关,而双磷酸盐类药物则是与风险增加有关。
  
  实际上,在10年时,不论开始时的BMD情况,相较于没有接受治疗的患者,进行副甲状腺手术的患者,髋骨骨折绝对风险降低64%,任何骨折的绝对风险降低24%,这个风险降低情况是显而易见的。
  
  10年时的髋骨骨折绝对风险,进行观察的患者是每千人有55.9例,进行副甲状腺手术的患者则是每千人有20.4例,使用双磷酸盐类药物者则是每千人有85.6例。
  
  10年时的任何骨折风险,进行观察的患者是每千人有206.1例,进行副甲状腺手术的患者则是每千人有156.8例,使用双磷酸盐类药物者则是每千人有302.5例。
  
  因为骨质疏松患者很常被开立双磷酸盐类药物,研究者根据开始时的BMD资料,持续分析患者发生骨折的可能性。
  
  治疗2年期间,相对于观察组,双磷酸盐类药物确实增加BMD值3.6%,相同时间内,副甲状腺切除术组的BMD值增加4.2%,两者相去不远。至于仅观察者的BMD,则是降低。
  
  但是,双磷酸盐类药物不仅没有防止骨折;还有证据显示伤害,骨质减少患者和骨质疏松症患者的骨折风险都增加,相对的,副甲状腺切除术则是与这两组患者的骨折风险降低有关。
  
  Yeh医师指出,副甲状腺切除术对于骨折风险的好处是,在术后2-5年的观察期间,BMD值一致地短期增加。
  
  副甲状腺手术对于骨质疏松患者的髋骨骨折最具预防效果。
  
  被问到使用双磷酸盐类药物治疗所达到的BMD增加为何不能降低骨折风险时, Yeh医师没有充分说明,承认它仍然是一个谜。
  
  他表示,举例来说,我们必须结论指出,即使BMD扫描看起来骨骼强壮,使用双磷酸盐类药物治疗的患者的骨格质量可能有某些状况,其骨骼可能是密集但是脆弱的。
  
  他指出,回溯性研究是永远不会完美的,但现在,原发性副甲状腺机能亢进症患者约有10%-25%进行了副甲状腺手术,至于没有手术者,当他们跌倒时可能会意外地髋骨骨折。我们可以做一些简单又不贵的小方法,来预防三分之二的骨折发生。
  
  他结论指出,所以,如果我们的报告有任何可用之处,就是表示确实没有可替代甲状腺手术的方式,我们的想法是,替代方案是不能被接受的。
  
  资料来源:http://www.24drs.com/
  
  Native link:Surgery Best to Reduce Fractures in Hyperparathyroidism

Surgery Best to Reduce Fractures in Hyperparathyroidism

By Pam Harrison
Medscape Medical News

Management of primary hyperparathyroidism with a simple surgical procedure to remove the benign tumor from the parathyroid significantly reduces fracture risk over time, whereas treatment with any of the bisphosphonates increases the risk in the same patients, a new observational study indicates.

"These patients have a 5% chance of fracturing over 10 years — I would be afraid of that — it's more common than a car accident," lead author Michael Yeh, MD, chief of endocrine surgery at the David Geffen School of Medicine, Los Angeles, California, told Medscape Medical News.

"And while we believed for years that the bisphosphonates were an acceptable alternative for the treatment of osteoporosis caused by primary hyperparathyroidism, our evidence shows that parathyroid surgery is really the only thing that works to decrease fracture risk," he asserts.

The study was published online April 4 in the Annals of Internal Medicine.

Only 20% of Patients Underwent Surgery

Dr Yeh and colleagues explain that primary hyperparathyroidism is a common endocrine disorder, affecting one in 400 women and one in 1200 men in the United States. Untreated primary hyperparathyroidism leads to loss of bone-mineral density (BMD) over time, raising concern about the development of osteoporosis and associated elevated fracture risk.

They used the Kaiser Permanente Southern California Laboratory Management System to retrospectively identify patients who had a biochemical diagnosis of primary hyperparathyroidism between 1995 and 2010.

Patients had classically defined primary hyperparathyroidism, identified as a serum total calcium level >2.63 mmol/L (>10.5 mg/dL) as well as an excess in parathyroid hormone (PTH) >65 ng/L.

BMD measurements were taken of the total hip and lumbar spine to the end of 2012.

Overall, the study involved 6272 patients with primary hyperparathyroidism, 36% of whom had osteopenia at baseline and 53% of whom had osteoporosis.

Some 22% of the group were treated with a bisphosphonate for a median duration of 55 months and another 22% underwent parathyroidectomy; the remaining 55% were kept under observation alone.

At a median follow-up of 4.5 years, investigators identified 940 fractures, 178 of them being fractures of the hip and 762 being fractures involving bones other than the hip.

Bisphosphonates Up Fracture Risk

"Across all time points, parathyroidectomy was associated with a reduced risk for any fracture, whereas bisphosphonates were associated with an increased risk," Dr Yeh and colleagues report.

Indeed, at 10 years, patients who had undergone parathyroid surgery had a 64% lower absolute risk for hip fracture and a 24% lower absolute risk for any fracture compared with patients who received no treatment, and this risk reduction was evident regardless of BMD at baseline.

The absolute risk for hip fracture at 10 years was 55.9 events per 1000 patients in those undergoing observation, 20.4 events per 1000 patients in those who had parathyroidectomy, and 85.6 events per 1000 patients in those treated with bisphosphonates.

The risk for any fracture at 10 years was 206.1 events per 1000 patients in those undergoing observation, 156.8 events per 1000 patients in those who had parathyroidectomy, and 302.5 events per 1000 patients in those treated with bisphosphonates.

Because patients with osteoporosis were more frequently prescribed a bisphosphonate, investigators went on to analyze the likelihood of patients experiencing a fracture according to BMD at baseline.

Over 2 years of treatment, the bisphosphonates did increase BMD by 3.6% relative to the observational group — not far short of the BMD increases of 4.2% seen in the parathyroidectomy group within the same time frame, compared with a reduction in BMD in those who underwent observation only.

Yet the bisphosphonates not only did not prevent fracture; there was evidence of harm, with increased fracture risk in both osteopenic and osteoporotic patients. In contrast, parathyroidectomy was associated with reduced fracture risk in both these populations.

Parathyroid Surgery the Best Option

The beneficial effect of parathyroidectomy on fracture risk "was concordant with short-term increases in BMD observed during the 2 to 5 years after surgery," Dr Yeh noted.

And parathyroid surgery was most protective in osteoporotic patients with regard to hip fracture.

Asked why an increase in BMD achieved with medical therapy with bisphosphonates didn't decrease fracture risk, Dr Yeh didn't have an adequate explanation, admitting that it remains a mystery.

"But we have to conclude that even though bones appear strong on BMD scanning, there is something wrong with the quality of the bone in patients treated with bisphosphonates. The bone could be dense but brittle," for example, he said.

He added: "Retrospective studies are never perfect, but right now, somewhere between 10% and 25% of people with primary hyperparathyroidism ever have parathyroid surgery, and for those who don't, they are going to fall down and fracture their hips unnecessarily, when we could do something small, easy, and cheap to prevent two-thirds of these fractures from occurring.

"So if our paper shows anything at all, it shows that there is really no viable alternative to parathyroid surgery. What we thought was an alternative is not acceptable," he concluded.

The study was funded by the National Institute on Aging, the Early Medical/Surgical Subspecialists' Transition to Aging Research, and its companion grant program, the American Geriatrics Society Jahnigen Career Development Award. Dr Yeh had no relevant financial relationships. Disclosures for the coauthors are listed in the article.

Ann Intern Med. Published online April 4, 2016.

    
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