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根据美国骨质研究学会第30届年会发表的第三期临床试验数据显示，一个研究中的新药denosumab，对于预防更年期后妇女骨折有明显的效果；这是人类单株抗体，它的好处在于耐受性佳，且投予方式是一年两次皮下注射。
Graham Russell 博士向Medscape医疗新闻叙述关于denosumab，它是抗体治疗，因此不同于其他治疗骨质疏松的用药，它能延缓骨质疏松的发展；Russell博士是英国牛津大学整形外科的骨骼肌肉药理专家，他主持了denosumab资料的发表。
多国研究每6个月评估使用Denosumab降低骨折发生的临床试验(FREEDOM)，共收纳7,868个年龄介于60至90岁，腰椎骨或整体T-scores为小于 -2.5和大于等于-4.0的妇女，每6个月随机接受denosumab 60毫克皮下注射或安慰剂，受试者同时接受每天1克的元素钙及400到800毫克的维他命D。
整体来说，有3,272位接受药物和3,206位接受安慰剂的病患完成为期36个月的治疗，Denosumab组降低了68%新骨折的发生，以及69%的临床上骨折（P<0.001）；除此之外，也降低了20%非脊椎性骨折风险以及40%髋骨骨折风险。
Russell医师表示，这项结果确实是很令人印象深刻，在这个骨质并不是最疏松的族群中，确实影响了三种骨折形式，且与现存药物一样有效；但是，因为并没有互相比较，所以很难说谁比较好。
在一项收纳441位病患的研究中，使用denosumab治疗组，其腰椎骨质密度增加了9.2%，髋骨骨质密度增加了6%（这两者的P<.001）；血中第一型胶原C碳末端胜肽，这是骨质溶解的指标之一（P<.001）。
两组之间整体不良反应率、严重不良反应、与导致停药的不良反应率都是差不多的；特别的是，中风、冠状动脉血管疾病、心房颤动、以及骨折延迟恢复率，药物治疗与安慰剂组是差不多的。
主要作者Steven Cummings医师在由Amgen公司召开的座谈会中表示，相较于双磷酸盐，我认为脊椎骨骨折率的下降是较大且较坚定的，这家公司是denosumab的制造厂商；Cummings医师指出，他们与zoledronic acid是相似的，但仍有差异，就是容易投予、没有与输注有关的症状、以及没有心房颤动的问题。Cummings医师是旧金山协调中心与旧金山加州大学医学教授。
研究者对于治疗骨质疏松症非双磷酸盐的处理选择感到兴奋，在Amgen的座谈会中，共同作者Ethel S. Siris医师表示，当我个人认为双磷酸盐是相当安全的药物时，我的病患中有些已经使用alendronate长达10年，与目前以alendronate进行的临床研究一样久，且我非常高兴，或许他们可以改使用非双磷酸盐药物治疗。Siris医师是医学学会临床医学与纽约哥伦比亚长老教会医学中心、哥伦比亚大学外科学Madeline C. Stabile教授。
Cumming医师表示，这个药物的关键好处是给药时程，对那些服药顺从性不佳的病患而言，我认为这是个非常吸引人的选择，从初级照护的观点看来，持续输注zoledronic acid以及需要专用空间来进行这件事是笨拙的，如果可以，就像接种流感疫苗一样简单将会更好。
这项研究由Amgen药厂赞助，Cumming医师接受Amgen药厂的赞助。
Investigational Drug Could Be an Alternative to Bisphosphonates for Osteoporosis
By Alison Palkhivala
Medscape Medical News
An investigational new drug called denosumab is showing remarkable efficacy in the prevention of fractures in postmenopausal women with osteoporosis, according to phase?3 data presented here at the American Society for Bone and Mineral Research 30th Annual Meeting. This human monoclonal antibody has the advantages of being very well tolerated and being administered as a twice-yearly subcutaneous injection.
"It's an antibody therapy and therefore different from most of the drugs that we have [for osteoporosis]," Graham Russell, MD, PhD, told Medscape Medical News about denosumab. "It neutralizes the major driver for osteoporosis development." Dr. Russell is a professor of musculoskeletal pharmacology at the Nuffield Department of Orthopaedic Surgery at the University of Oxford, in England. He moderated the session in which the data on denosumab was presented.
For the multinational Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months (FREEDOM) trial, 7868 women between 60 and 90 years of age with lumbar spine or total tip T-scores between ?.5 and ?.0 were randomized to receive denosumab 60?mg by subcutaneous injection every 6 months, or matching placebo. Participants also received 1?g daily of elemental calcium and 400 to 800?mg daily of vitamin?D.
Overall, 3272 patients taking active therapy and 3206 patients taking placebo completed a full 36 months of therapy. Treatment with denosumab was associated with a 68% reduced risk for new vertebral fracture, and a 69% reduced risk for clinical vertebral fracture (P?< .001). In addition, the risk for nonvertebral fracture was reduced by 20% (P?= .011) and the risk for hip fracture was reduced by 40% (P?= .036).
"The results are really impressive," said Dr. Russell. "In a population that is not the most osteoporotic, it actually affects all 3 fracture types at least as well as existing drugs. it's hard to say whether it's better because nothing's been compared head-to-head."
In a substudy involving 441 patients, bone mineral density was increased by 9.2% at the lumbar spine and by 6% at the hip with denosumab therapy (P?< .001 for both). There was also a 72% reduction in serum type?I collagen C-telopeptides, a marker of bone resorption (P?< .001).
The rate of overall adverse events, serious adverse events, and adverse events leading to discontinuation were similar in both groups. In particular, the rates of stroke, coronary heart disease, atrial fibrillation, and delayed fracture healing were similar for those on active therapy and those on placebo.
"Compared with the bisphosphonates that are out there, I think the reduction in vertebral fracture rates is larger and more robust," said lead investigator Steven Cummings, MD, during an information session organized by Amgen, the manufacturer of denosumab. "They're similar to [zoledronic acid], but there the difference?.?.?. is ease of administration, lack of symptoms related to infusion, and [lack of] atrial fibrillation." Dr. Cummings is founding director of the San Francisco Coordinating Center and a professor of medicine at the University of California at San Francisco.
The investigators are excited about the prospect of a nonbisphosphonate option for the management of osteoporosis. During the Amgen information session, coauthor Ethel S. Siris, MD, said: "While I personally think bisphosphonates are pretty darn safe drugs, some [of my patients] have been on alendronate for 10 years, which is as far as the clinical trials have gone with alendronate, and I am very pleased that maybe they can switch to a nonbisphosphonate." Dr. Siris is the Madeline C. Stabile professor of clinical medicine at the College of Physicians and Surgeons of Columbia University, Columbiaresbyterian Medical Center, in New York.
But the key benefit of this drug is its dosing schedule. "In patients who have had a history of poor compliance on oral pills, I think this is a very attractive option," said Dr. Cummings. "From the perspective of primary care practice, the idea of setting up infusions [of zoledronic acid] and setting aside a room to do that is kind of clumsy, and it's a whole lot easier?.?.?. to give what is essentially [like a] flu shot."
The study was funded by Amgen, and Dr. Cummings has received funding from Amgen.
American Society for Bone and Mineral Research (ASBMR) 30th Annual Meeting: Abstract 1286. Presented September 16, 2008.