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ESTES PARK, Colorado (EGMN) –Poor adherence accounts for more than 90% of all cases of failure to respond to osteoporosis therapy as evidenced by declining bone density or a fracture.

Lack of medication efficacy, on the other hand, is the least likely of the common causes for failure to respond. It ranks behind calcium/vitamin D deficiency, hyperthyroidism and other comorbid conditions, and the use of corticosteroids or other osteoporosis-inducing medications to treat comorbid conditions, Dr. Michael T. McDermott said at a conference on internal medicine sponsored by the University of Colorado.

He singled out failure to respond to treatment as one of the five top challenges in osteoporosis management today. Here are the other challenges highlighted by Dr. McDermott, professor of medicine and director of endocrinology and diabetes practice at University of Colorado Hospital, Denver:

Comorbid osteoporosis-inducing medications. Glucocorticoids top the list. They simultaneously reduce bone formation and increase bone resorption, resulting in quick bone loss in patients taking steroids. Serious consideration should be given to prescribing osteoporosis therapy in any patient who has ever been on 5 mg/day or more of prednisone for at least 3 months, according to Dr. McDermott.

Compelling 18-month data from a randomized trial of teriparatide versus alendronate for the treatment of glucocorticoid-induced osteoporosis showed teriparatide to be the clear winner, both in terms of increased bone density and fewer vertebral fractures (N. Engl. J. Med. 2007;357:2028-39). The soon-to-be-published 3-year follow-up data confirm this.

“As we move forward, teriparatide may be one of our go-to medications for our more severe cases of glucocorticoid-induced osteoporosis,” Dr. McDermott said.

He added that the No. 2 class of medications causing osteoporosis may come as a surprise to many physicians: anticonvulsants. “Anticonvulsant-induced osteoporosis hasn’t been recognized as much, but it’s emerging as quite important. It’s a much bigger problem with phenobarbital, [phenytoin], and [carbamazepine] than with the newer anticonvulsants,” he said.

“The best recommendation is, if you have a person on chronic anticonvulsant therapy, monitor their bone density, monitor their calcium, and rather than having a goal of 1,000 IU/day of vitamin D, they should be on 2,000-4,000 IU/day. I think that’s reasonable. There’s no data on bisphosphonate use in patients on anticonvulsants, so I’d just have a high index of suspicion and make sure you’re giving them good vitamin D therapy,” he continued.

Atypical fractures of the femoral diaphysis. These fractures are the most recent and worrisome development in the osteoporosis field. Many experts now informally advocate a bisphosphonate therapy holiday after 5 years of use in an effort to avoid these fractures.

Osteonecrosis of the jaw. This condition is marked by nonhealing exposed bone for at least 8 weeks following an invasive dental procedure such as tooth extraction. Dr. McDermott said that he doesn’t see it often, but he fields many phone calls about it from physicians and dentists.

The great majority of cases have occurred in patients on high-dose intravenous bisphosphonate therapy for underlying bone cancer; oral bisphosphonates have not been shown to cause the disorder. Nevertheless, when Dr. McDermott is ready to start a patient on a bisphosphonate, he asks if a tooth extraction or dental implant is planned; if so, he’ll wait to start the drug until after the procedure.

“If a person is on a bisphosphonate and a dentist calls me and says, ‘I will not do this dental work while your patient is on that medication,’ I’ll stop it for 3 months,” he said. “There’s no data to support what I’ve just said. However, we know that the resolution of effect for these medications is 6-12 months. People will not lose bone density by stopping their medicine for only 3 months, and it gets the dentist to do the surgery. It’s a compromise position that works. You can do it or you can hold your ground.”

Osteoporosis medications and renal disease. Citing a lack of safety data, the U.S. Food and Drug Administration recommends against using bisphosphonates in patients with an estimated glomerular filtration rate (eGFR) below 30 mL/min per 1.73 m2. However, limited experience indicates that treatment is reassuringly safe and effective in patients with an eGFR of 15-30 mL/min per 1.73 m2, according to Dr. McDermott.

“I do caution against antiresorptive therapy in patients with an eGFR below 15 mL/min –stage 5 chronic kidney disease –because it may predispose to adynamic bone disease,” he added.

Dr. McDermott disclosed serving on the speakers bureaus of several pharmaceutical companies.

Copyright (c) 2009 Elsevier Global Medical News. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.

科罗拉多 (EGMN)——超过90%的骨质疏松症治疗无应答病例都是因依从性过差所致，骨密度下降或骨折即提示治疗无应答。

 

Michael T. McDermott博士在美国科罗拉多大学举办的一次内科学会议上指出，“另一方面，药物治疗疗效差是导致骨质疏松症治疗无应答的最不常见原因。比这更常见的原因包括：缺钙或维生素D、甲状腺功能亢进、其他合并症以及为治疗合并症而采用的皮质激素或其他可诱导骨质疏松症的药物。”

 

McDermott博士是美国科罗拉多大学医院的医学教授，任内分泌与糖尿病科主任，他将治疗无应答列为当今骨质疏松症治疗面临的五大挑战之一。McDermott博士列举的另外四大挑战如下：

 

为治疗合并症而采用的可诱导骨质疏松症的药物。以糖皮质激素最为常见。糖皮质激素在抑制骨形成的同时还会增加骨吸收，从而导致服用类固醇激素的患者迅速出现骨丢失。McDermott博士提醒道，对于曾经接受过强的松治疗至少达3个月的患者，若剂量达到或超过5 mg/天，则应慎重考虑予以骨质疏松症治疗。

 

有研究者对特立帕肽与阿仑膦酸盐治疗糖皮质激素诱导的骨质疏松症开展了一项随机试验，非常有说服力的18个月的数据表明，无论是从骨密度的增幅还是椎体骨折的发生率来看，特立帕肽都显著优于阿仑膦酸盐(N. Engl. J. Med. 2007;357:2028-39)。即将发表的3年随访数据也证实了这一结论。

 

McDermott博士认为，“在未来的临床实践中，特立帕肽很可能成为治疗糖皮质激素诱导的骨质疏松症重症患者的预备药物之一。”

 

很多医生可能都会惊讶，导致骨质疏松症的第二大类药物居然是抗惊厥药。McDermott博士称，“目前人们对抗惊厥药诱导的骨质疏松症认识还不够，但其重要性非常值得关注。相对于新型抗惊厥药，传统药物如苯巴比妥、苯妥英、卡马西平等导致骨质疏松症的可能性更大。”

 

McDermott博士继续指出，“最佳建议是，如果患者长期接受抗惊厥治疗，则应监测其骨密度和血钙浓度。维生素D的常规补充剂量1000 IU/天可能偏低，应加大剂量至2000-4000 IU/天。我认为这种用法是合理的。目前尚无有关双膦酸盐用于接收了抗惊厥治疗的患者的资料，因此现在只能高度关注，同时确保患者接受了足够的维生素D治疗。”

 

非典型性股骨干骨折。这类骨折可谓是骨质疏松症领域的新成员，其出现令人感到棘手。目前许多专家建议在双膦酸盐治疗5年后暂时停用一段时间以避免这类骨折的发生，当然这种做法是非正式的，还有待证实。

 

颌骨坏死。该病的特征是，在诸如拔牙一类的创伤性牙科操作后，骨外露不愈合至少持续8周。McDermott博士称其亲眼见过的病例并不多，但常常接到其他医生和牙医的电话来询问此病。

 

绝大部分病例都出现在为了治疗潜在骨癌而接受大剂量双磷酸盐经静脉治疗的患者中；口服双磷酸盐不会导致该病。但每当McDermott博士准备对患者采取双磷酸盐治疗时，他都会询问患者是否有拔牙或种植牙的计划；如果有，他会等到患者完成拔牙或种植牙之后再开始使用双磷酸盐。

 

 “如果我的患者正在接受双磷酸盐治疗，而牙医打电话告诉我，‘你的患者正在使用双磷酸盐，我不能对其进行这项牙科操作。’那么我会停用双磷酸盐3个月。” McDermott博士解释道，“我的这种做法尚无任何证据支持。但我们知道双磷酸盐的药效消退需要6～12个月。患者不会因停药仅3个月就导致骨密度下降，但这样做牙医就有时间完成他的手术。这是一种折中的做法，但行之有效。当然，您可以照着我说的做，也可以坚持己见。”

 

骨质疏松症治疗药物与肾病。鉴于缺乏相应的安全性数据，美国食品药品管理局建议不要对肾小球滤过率估值(eGFR)低于30 mL/(min•1.73 m2)的患者使用双磷酸盐。但McDermott博士指出，有限的临床运用经验显示，双磷酸盐治疗用于eGFR 在15～30 mL/(min•1.73 m2)之间的患者是安全且有效的。

 

McDermott博士补充道，“但我仍然建议对于eGFR低于15 mL/(min•1.73 m2)，即5期慢性肾病患者，应慎用骨吸收抑制药。”

 

McDermott博士称其为多家制药企业的讲师团成员。

 

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