手術對於減少副甲狀腺機能亢進症之骨折效果最佳


  【24drs.com】一篇新發表的觀察型研究指出,原發性副甲狀腺機能亢進症之處置,採用從副甲狀腺移除良性腫瘤的簡單手術,可顯著降低一段時間的骨折風險,而若以任何雙磷酸鹽類藥物治療相同患者,則會增加前述風險。
  
  第一作者、加州洛杉磯分校大衛格芬醫學院內分泌外科主任Michael Yeh醫師表示,這些患者10年期間的骨折機率約為5%,這是令人害怕的-因為比車禍還常見。
  
  他斷言,雖然數年來我們相信,雙磷酸鹽類藥物可用於治療原發性副甲狀腺機能亢進症引起的骨質疏鬆症,我們的證據顯示,副甲狀腺手術是唯一可以降低骨折風險的方法。
  
  這篇研究線上發表於4月4日內科醫學誌。
  
  Yeh醫師等人解釋,原發性副甲狀腺機能亢進症是常見的內分泌疾病,在美國影響約1/400的女性與1/1200的男性。原發性副甲狀腺機能亢進症若未治療,會導致骨質密度(BMD)隨著時間流失,引起發生骨質疏鬆與相關骨折風險增加的顧慮。
  
  他們使用Kaiser Permanente Southern California Laboratory Management System回溯檢視在1995-2010年間,生化診斷有原發性副甲狀腺機能亢進症的患者;原發性副甲狀腺機能亢進症患者的傳統定義是,血清總鈣質數值>2.63 mmol/L(>10.5 mg/dL) 以及過高的副甲狀腺素值(PTH):>65 ng/L。
  
  在2012年底針對總髖骨與腰椎測量BMD。整體而言,這篇研究納入6,272名原發性副甲狀腺機能亢進症患者,有36%在開始時有骨質減少,其中53%有骨質疏鬆。
  
  這些患者中,22%使用一種雙磷酸鹽類藥物治療,療程中位數為55個月,其他22%進行了副甲狀腺切除術,其餘55%則是僅有維持觀察。
  
  中位數4.5年的追蹤期間,研究者確認940例骨折,其中178例是髖骨骨折,762例是髖骨之外的其他部位骨折。
  
  Yeh醫師等人報告指出,在各個時間點,副甲狀腺切除術都與骨折風險降低有關,而雙磷酸鹽類藥物則是與風險增加有關。
  
  實際上,在10年時,不論開始時的BMD情況,相較於沒有接受治療的患者,進行副甲狀腺手術的患者,髖骨骨折絕對風險降低64%,任何骨折的絕對風險降低24%,這個風險降低情況是顯而易見的。
  
  10年時的髖骨骨折絕對風險,進行觀察的患者是每千人有55.9例,進行副甲狀腺手術的患者則是每千人有20.4例,使用雙磷酸鹽類藥物者則是每千人有85.6例。
  
  10年時的任何骨折風險,進行觀察的患者是每千人有206.1例,進行副甲狀腺手術的患者則是每千人有156.8例,使用雙磷酸鹽類藥物者則是每千人有302.5例。
  
  因為骨質疏鬆患者很常被開立雙磷酸鹽類藥物,研究者根據開始時的BMD資料,持續分析患者發生骨折的可能性。
  
  治療2年期間,相對於觀察組,雙磷酸鹽類藥物確實增加BMD值3.6%,相同時間內,副甲狀腺切除術組的BMD值增加4.2%,兩者相去不遠。至於僅觀察者的BMD,則是降低。
  
  但是,雙磷酸鹽類藥物不僅沒有防止骨折;還有證據顯示傷害,骨質減少患者和骨質疏鬆症患者的骨折風險都增加,相對的,副甲狀腺切除術則是與這兩組患者的骨折風險降低有關。
  
  Yeh醫師指出,副甲狀腺切除術對於骨折風險的好處是,在術後2-5年的觀察期間,BMD值一致地短期增加。
  
  副甲狀腺手術對於骨質疏鬆患者的髖骨骨折最具預防效果。
  
  被問到使用雙磷酸鹽類藥物治療所達到的BMD增加為何不能降低骨折風險時, Yeh醫師沒有充分說明,承認它仍然是一個謎。
  
  他表示,舉例來說,我們必須結論指出,即使BMD掃描看起來骨骼強壯,使用雙磷酸鹽類藥物治療的患者的骨格品質可能有某些狀況,其骨骼可能是密集但是脆弱的。
  
  他指出,回溯性研究是永遠不會完美的,但現在,原發性副甲狀腺機能亢進症患者約有10%-25%進行了副甲狀腺手術,至於沒有手術者,當他們跌倒時可能會意外地髖骨骨折。我們可以做一些簡單又不貴的小方法,來預防三分之二的骨折發生。
  
  他結論指出,所以,如果我們的報告有任何可用之處,就是表示確實沒有可替代甲狀腺手術的方式,我們的想法是,替代方案是不能被接受的。
  
  資料來源: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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