In this last section of the osteoporosis case we will look at the treatment and we will consider the case presentation and make some comments so regarding the treatment there is encouraging data that shows that treatment for osteoporosis can decrease fracture risk by nearly fifty percent calcium supplementation of 1200 milligrams per day in females greater than 17
Years of age along with at least 800 iu’s of vitamin is recommended and vitamin d enhances calcium absorption from the small intestine because serum calcium concentrations are closely regulated if losses of calcium in urine and feces are not replacing the diet parathyroid hormone secretion will increase to compensate this secondary hyperparathyroidism can lead to
Continued small losses of calcium to these measures may be added muscle strengthening and balance exercises and hip protectors to prevent falls and hip fractures medical therapy is divided between the following two major classes of agents anterior absorptive drugs which are drugs that inhibit osteoclasts taking activity and anabolic drugs these drugs that act on
The osteoblasts to stimulate bone formation so first let’s talk about the anti resorb tus estrogen is a powerful agent to treat postmenopausal women with osteoporosis working by inhibiting signaling of rank ligand between the osteoblasts and the osteoclast but the women’s health initiative has shown that long-term use of estrogen and progesterone is associated
With twenty six percent increase in the risk of invasive breast cancer consequently most physicians will be reluctant to use estrogen to treat osteoporosis and of course it is contraindicated in women with a history of breast cancer selective estrogen receptor modulators or serms such as tamoxifen and raloxifene like estrogen block release of cytokines from
Osteoblasts while both of these serms block estrogen action on the breast tamoxifen is associated with a greater risk of developing endometrial cancer raloxifene does not have this adverse effect on the endometrium molecular studies have revealed that while raloxifene and estrogen bind to the same region of the estrogen receptor they cause different changes in the
Three-dimensional structure of the receptor bisphosphonates have become the most widely used anti ribs orbit of therapy for osteoporosis these drugs are carbon substituted derivatives of inorganic pyrophosphate or ppi that like ppi bind tightly to hydroxyapatite crystals they impede bone resorption by blocking osteoclast attachment to bone and by hastening program
Cell death oral agents include alendronate and resend earn eight and an intravenous agent soul and ronak acid many experts recommend discontinuing by phosphonate treatment for after five years with the dividend that in the ensuing five years there is minimal bone loss erosive esophagitis used to be fairly common with daily by phosphonate dosing but now with weekly
Or monthly regimens it has receded as an issue serious but rare is osteonecrosis of the jaw which is more common after oral surgery but can occur spontaneously austin across of the jaw is usually associated with high-dose soul and ronak acid for treatment of myeloma or other bone cancers with a full understanding of the role of rank ligand in osteoclast genesis it
Is clear that rank l is a potential site for anti resorption therapy the monoclonal antibody denosumab exploits this opportunity by binding to rank l thus limiting its action in stimulating bone absorption in a clinical trial denno some ab was administered by one subcutaneous injection and suppressed bone absorption by up to 81 percent for as long as six months
Once the effects of denosumab have worn off however bone turnover returns to pretreatment levels the lysosomal enzyme cathepsin k which is involved in enzymatic degradation of bone is now targeted by a specific inhibitor oh done a cat it while the drug suppresses bone absorption it does not affect osteoclast survival now let’s talk about anabolic therapy anabolic
Therapeutic options are more limited than aunty absorbed in therapies first and foremost as pth or parathyroid hormone the n-terminal fragment termed terry para tied the parathyroid gland senses changes in extracellular calcium through a cell surface calcium sensing receptor consequently pth plays a vital role in regulating calcium homeostasis increased serum
Calcium decreases pth release while decreasing levels of calcium trigger pth release pth also stimulates 1 alpha hydroxylase activity in the kidney increasing the formation of the active form of vitamin d 125 dahak’s the hydroxyl d although constant high levels of pth as in primary hyperparathyroidism have long been known to cause bone resorption and ostia titus
Fibrosis cystica low and intermittent doses of pth promotes bone formation one observation that accounts for the anabolic effect of low-dose pth is an increase in the lifespan of mature osteoblasts there may be other effects of low-dose pth that have yet to be defined low-dose tara tight administered subcutaneously on a daily basis increases bone mass and reduces
Occurrence of fractures because of a concern for development of osteosarcoma it is recommended that pth used be restricted to two years another anabolic therapy is in clinical trials as inhibition of wn t antagonists especially dkk1 this inhibitor bhq 880 blunts the effect of wn t on causing bone accretion blocking dkk1 action therefore allows the anabolic effect
Of wn t to be expressed and finally some comments on the case presentation which was a first present eight the case was given in the first part of the videos if you look in this section our patient is at risk for additional fractures based on history of vertebral compression and the t-score in the osteoporosis range she is a candidate for alendronate or rescind
Renee to be administered for five years a calcium intake of 1200 milligrams per day preferably in her diet but with supplements if necessary is important in determining 25-hydroxyvitamin d levels is also advised and if flow she should receive vitamin d supplementation of 800 to 1,000 i use per day and a dexa scan should be repeated in a one year and then every two
Years to assess the efficacy of by phosphonate therapy
Transcribed from video
Osteoporosis – Treatment options By Simon R. Downes – Med School Radio – USICO Care
