important menopause information
Once you have been diagnosed with osteoporosis, have had an osteoporotic fracture, or it has been determined that your FRAX score is high, treatment with medication is indicated. So many women have misconceptions about the medications, their risks and benefits. Let’s go through the categories of medication and options in each category.
This is a category of drugs that decreases re-absorption of old bone. We all have osteoclasts that are cells in our bones that remove old bone, and osteoblasts that put down new bone. Prior to menopause, the osteoblasts are more active than the osteoclasts, and new bone is formed at a higher rate than bone is lost. This changes at menopause, and with other conditions of low estrogen such as anorexia, prolonged lactation, and use of aromatase inhibitors. . Bisphosphonates work by decreasing the function of the osteoclasts.
There are 4 bisphosphonates: alendronate, risedronate, ibandronate, and zoledronate.
These drugs can be given orally or IV. All bisphosphonates decrease vertebral fractures from 35-65%. Both alendronate and zoledronate significantly reduce hip fractures also, and risedronate reduces non-vertebral fractures. If taken orally, the drug must be taken on an empty stomach with 8 ounces of water, and patients are advised to sit or stand for 30-60 minutes after ingestion to avoid reflux that could cause esophageal irritation. If the medication is taken with food or other drugs, the absorption of the drug is diminished and it will be less effective. These drugs remain active in the bone for some time after discontinuation of the drug. Alendronate specifically will remain in the bone for 5 years after the last dose, and the bone density will usually decline slowly during this time. This allows for patients to take drug holidays, without losing most of the benefits gained. Risedronate users had significant loss of bone in the first year after discontinuation.
Zolendronate is a once-yearly infusion. It cannot be given to patients with acute renal failure or a creatinine clearance of less than or equal to 35 mL/min.
Press reports have over-emphasized the side effects of this class of drugs. Side effects can include musculoskeletal aches and pains, gastrointestinal irritation and ulcers of the esophagus. More severe side effects including osteonecrosis of the jaw and atypical fractures of the femur are very rare, occurring in about 1/10,000 years of use. Since most women who take these drugs have a 20% risk of any fracture, and a greater than 3% risk of a hip fracture in the next 10 years, the risk/benefit ratio is far in favor of a benefit. Because of the long-term duration of effect of the bisphosphonates, it does not make sense to stop the drug during a dental procedure. It does make sense to have frequent dental exams while taking the medication, as osteonecrosis of the jaw, if caught early, is treatable. It also makes some sense to have any invasive dental work completed before starting bisphosphonate use.
Dosing of the bisphosphonates vary from orally weekly to monthly, and IV from every 3 months to yearly, depending on the drug. Patients with upper GI problems might consider intravenous administration, or a short-term trial of an oral agent.
Selective estrogen agonists/antagonists:
Raloxifene is a selective estrogen receptor modulator, or a SERM. This type of drug was designed by scientists to act like estrogen in certain parts of the body, while acting as an anti-estrogen in other parts of the body. Raloxifene acts like estrogen in the bone. Because of this, it is an anti-resorptive drug, preventing the resorption of old bone. It has been shown to reduce vertebral fractures. In the breast, raloxifene acts as an anti-estrogen, so a beneficial side effect is that it reduces the risk of postmenopausal breast cancer in women who have osteoporosis, even if they are at high risk of developing breast cancer.
This drug is taken orally, once a day and is usually well-tolerated. It can increase hot flashes, especially in women who are newly menopausal and who are still having vasomotor symptoms.
More serious side effects include blood clots in the legs and deaths from stroke, although the incidence of stroke is not increased. This drug is especially beneficial for women with osteoporosis who are at increased risk of breast cancer. Five years of use will reduce the subsequent risk of breast cancer by at least 50%.
Denosumab is a mono-clonal antibody that works in the cascade of molecules that affect the function of the osteoclast. The drug inhibits a pathway that leads to de-activation of the osteoclast, and thus less bone is reabsorbed. This drug has been available since 2010, and has been shown to reduce vertebral fractures by 68% and hip fractures by 40%. It is given subcutaneously by injection twice a year. Prior to administration, it is important to check the calcium level of the patient.
This drug is very well tolerated. It is believed that the risk of osteonecrosis of the jaw and atypical femoral fractures is very low. There is a significant increase in infections that were noted in clinical trials, but in practice, this risk is very low. Occasionally a patient will note musculoskeletal pain after injection, but again, this is infrequent.
Because the bone density can decrease significantly after this drug is stopped, and the fracture risk does increase in the first year, discontinuation of drug should be followed by a maintenance medication.
Calcitonin is administered as a nasal spray has been used for the reduction of vertebral fractures, but it is not as effective as other agents. It can be effective in women who have painful vertebral fractures by diminishing the pain.
Teriparatide or recombinant human parathyroid hormone stimulates the osteoblasts to produce more bone, therefore it is considered an anabolic (growth) hormone, rather than an anti-resorptive agent. It improves the micro-architecture of the bone, making it stronger. The drug is given daily and subcutaneously, therefore it is self-administered by the patient, and can only be given for two years. In animal studies, use more than two years increased the incidence of bone cancers, but this has not been seen in humans. After discontinuation of the drug, a patient must be switched to another medication to maintain the benefit.
This medication has been found to decrease the risk of vertebral and non-vertebral fractures. Side effects include nausea, dizziness, and muscle cramps, but since it is a daily dose, it can be discontinued easily.
Parathyroid hormone is often used in cases where the bone density decreases despite use of other drugs, or after a fracture has been sustained. Because it can only be used for two years, it must be part of a long-term strategy.
Estrogen is a potent anti-resorptive agent, and it is well known that bone density decreases significantly in the first five years of menopause. In the Women’s Health Initiative, vertebral and hip fractures were reduced about 35% by hormone therapy. Hormone therapy is approved for the prevention of osteoporosis in women at risk. Even very low dose estrogen patches have a benefit in the reduction of osteoporosis, although the benefit is dose-related. Hormone replacement therapy should be an important part of the conversation as a women enters menopause and considers her symptoms and goals, her family history and risk factors, and the type of treatment most suited to her individual situation. Most women can take combined estrogen and progesterone for at least five years with no increase in breast cancer, and longer if she is using estrogen only. After discontinuation of HRT, loss of bone density can be rapid and the benefit can be lost in two years, so monitoring bone density and adding another drug should be considered.
In the next chapter, we will look at drug holidays and try to put concerns about serious side effects in perspective.
Foxhall OB-Gyn Associates
The. American College of Obstetricians and Gynecologists. Practice Bulletin. Osteoporosis,
Number 129, September 2012