Osteoporosis derives from the Greek meaning “porous bones. ” This disease causes porosity and brittleness of the bone due to the excessive loss of protein, mineral content and calcium. Osteoporosis is known to affect both men and women of all races, although Caucasian and Asian postmenopausal women are at highest risk for developing osteoporosis.
Generally, osteoporosis is known as the “silent disease” because there are no symptoms during the early stages of bone loss. But it is common for people to suffer from various fractures or broken bones before being diagnosed. Osteoporotic fractures occur in areas where healthy people would not normally suffer fractures. For example, these fragility fractures occur in the wrist, hip, rib and spinal column. It has been reported that fewer than 20% of fracture patients in Canada currently undergo diagnosis or adequate treatment for osteoporosis. Treatment and diagnosis are imperative for the well being of the patient since Osteoporosis Canada claims that 28% of women and 37% of men who suffer a hip fracture will die within the following year.
There are various treatments for osteoporosis but the most widely prescribed medications are bisphosphonates. Bisphosphonates are so named for the two phosphate groups (PO3) present in the molecule. Bisphosphonates require these phosphate groups in order to properly function as drugs. These drugs are responsible for preventing loss of bone mass.
Bones undergo a continuous process of remodeling. The remodeling cycle consists of bone resorption followed by bone formation. During bone resorption, specialized cells known as osteoclasts chew up bone material leading to bone loss. However, another set of specialized cells called osteoblasts are responsible for laying down bone material required for bone formation. The purpose of this continuous cycle is to ensure that bone architecture can be adjusted in order to accommodate mechanical needs as well as repair microdamages in bone matrix.
Now back to bisphosphonates. What is the mechanism of action for these drugs? Well, the skeleton takes up bisphosphonates preferentially during bone formation. Bisphosphonates become part of the newly formed bone since their chemical structure allows them to strongly bind to hydroxyapatite. Hydroxyapatite is a complex calcium phosphate mineral and element found in bone. Due to this strong interaction between the hydroxyapatite and bisphosphonates, the drugs can stay embedded in bone years withstanding numerous cycles of remodeling. In fact, it is common for patients to be exposed to its effects long after discontinuing this treatment.
Medical officer at FDA’s center for Drug Evaluation and Researcher, Dr. Marcea Whitaker warned, “Bisphosphonates have been proven very effective in protecting against bone fractures in clinical trials lasting three to four years. But it's still unknown whether the benefit lasts longer than that in decreasing the risk of fractures.” In addition, the FDA has ordered that a safety warning appear on the bisphosphonate label. Indeed, there seems to be an increased risk of unusual thighbone fractures, severe jawbone decay and esophageal cancer. Due to these associations, the FDA suggests that physicians should reconsider the length of time that this treatment is prescribed.
Prolia is another treatment for osteoporosis. The FDA approved this treatment in June 2010. But don’t be fooled, Prolia also goes by the name Xgeva! And yet, perhaps Prolia and Xgeva are better known by the generic name: denosunab. Prolia is a specific RANKL inhibitor. RANKL (receptor activator of nuclear factor kappa-B ligand) functions as a key factor for osteoclast differentiation and activation. This means that when Prolia targets and inhibits RANKL, osteoclasts will not be able to chew away bone material.
Prolia is administered as a single subcuntaneous injection every six months. FDA warns that Prolia can cause serious side effects. Side effects include and are not limited to skin problems, allergic reactions, infections, severe jawbone problems, unusual thighbone fractures and hypocalcemia. Since hypocalcemia leads to low calcium levels in the blood, physicians usually prescribe calcium and vitamin D in order to counteract these effects. Prolia is rather novel, therefore, it is not yet known whether its continued use over a long period of time may successfully cause slow healing of broken bones.
Recently, a clinical trial was published in the world’s leading medical journal, The Lancet. A new combination drug therapy might be the best treatment for osteoporosis in postmenopausal women. It was discovered that when administering the combination of drugs, teriparatide and denosumab, an increase in bone mineral density was observed. Teriparatide is a bone building, anabolic drug while denosumab acts to halt bone loss. The lead author of this clinical study, Benjamin Leder, stated, “our results demonstrate that the combination of denosumab and teriparatide increases bone density more than either individual therapy.” The explanation for this finding is probably because denosumab is able to potently block bone loss even when administered with the bone-building drug, teriparatide. Despite these findings, further investigation is required in order to assess the effectiveness and safety of this combination therapy.
