Men's Osteoporosis Support GroupDenosumab (Prolia) to treat osteoporosis The FDA recently approved Prolia (denosumab) for treatment of postmenopausal osteoporosis. There are several Updates on this site pertaining to denosumab before it was approved by the FDA. Here is one from 2009 that includes two review articles on the topic with somewhat differing conclusions, particularly regarding its anti-fracture efficacy and the possibility of infections as a side effect. The article featured below will have some additional information of Prolia and several other osteoporosis treatments. Endocr Pract. 2010 Mar 29:1-23. [Epub ahead of print]. New Treatment Modalities in Osteoporosis. Canalis E. PMID: 20350910. There is also free full text of this article available. From the abstract you will see that this article is an update on several new treatments for osteoporosis, including denosumab. I suggest you read the free full text to get a good idea of what new treatments are there now, or may soon become available. Several of the medications are female-specific, so I won't discuss them. I will, however, mention some of the highlights of those medications that are gender neutral. Note that Prolia is only FDA approved for postmenopausal women, but presumably it could be given off label to men. The same would go for cathepsin K inhibitors. Prolia 1. Both the bisphosphonates and Prolia function by preventing bone resorption. Canalis notes there are differences in how they do that, "In contrast to bisphosphonates that inhibit osteoclast function and survival, denosumab acts by blocking RANK-L, decreasing the formation of osteoclasts." [Emphasis is mine in all quotations]. 2. In phase III clinical trials, "Compared to placebo, denosumab decreased the incidence of vertebral fractures by 68% after three years; and a significant reduction in fractures was noted as early as after 1 year of treatment." Note that hip fractures were also reduced by 40%. 3. The one serious adverse event that occurred more frequently in the denosumab group than placebo was cellulitis. This can have quite serious consequences, so it is a side effect worth following to see if more cases are found with additional people on the medication. Canalis notes that other trials also found increased infections which might stem from the fact that RANK-L and RANK are also expressed by lymphoid cells These are immune cells that fight infections which might be counteracted by denosumab. 4. Another potentially important finding was, "A preliminary study reporting the results of bone biopsies from the phase III pivotal fracture trial demonstrated absence of dual tetracycline labels in biopsies from patients receiving denosumab, a sign of markedly suppressed bone remodeling." Note that osteonecrosis of the jaws is suspected of occurring in some individuals taking bisphosphonates, mostly for high-dose, i.v. usage for cancer treatment. However, rarely some individuals on oral bisphosphonates also have gotten this serious side effect. It is felt that overly suppressed bone remodelling is the cause, thus a reason to be suspicious and watchful regarding Prolia usage long term, although no osteonecrosis cases have been reported yet. 5. Potential advantages of Prolia over bisphosphonates, ". . . include increased compliance since it would be administered in a physician's office, lack of skeletal accumulation and the fact that it is not cleared by the kidney, making it a possible alternative to bisphosphonates in individuals with impaired renal function . . ." Cathepsin K inhibitors. Several of these are mentioned, including odanacatibk balicatib and relacatib. They are in various phases of clinical trials, but not yet FDA approved. They function by degrading type I collagen via osteoclasts, so inhibiting them would reduce bone breakdown without affecting bone formation. Src Kinase Inhibitors. These play a role in osteoclast survival and activity. Saracatinib is an oral competitive inhibitor of Src kinase that inhibits bone resorption that has been given to men in a phase I clinical trial. It dose-dependently decreased bone resorption markers without significant adverse events. Novel anabolic therapies. Teriparatide. This is the 1-34 amino acid fragment of human parathyroid hormone that is FDA approved and has been shown to increase bone mineral density and reduce fractures by increasing mature osteoblasts. It currently is available only in daily injection form but research is testing several other modalities. These include oral, transdermal and intranasal. The article mentions several other anabolic agents that are in various stages of testing. Since these aren't yet near FDA approval, I'll let you read about them in the full text article if you wish. It appears that there could be several new bone-forming medications on the market eventually. How to get free full text online articles if not on PubMed. PubMed is the main source of medical research articles online, and the first source I check. You will often find, especially for more recent articles, that the abstract will be the only information that is available. But PubMed will also have the free full text links for some recent research, and for many other older articles, right there with the abstract. If you don't see a link for the free full text article, don't give up. Go to one of the good online search engines such as Google, Yahoo, Bing, etc. Copy and paste the full name of the article for which you have the abstract from PubMed into the search engine query block, and you will often find that there are copies of the free full text somewhere else than PubMed online.
|
|
|