WOMEN AND OSTEOPOROSIS

     Though certainly not unique to women, osteoporosis affects some 40% of women by the age of fifty and only 13% of men by the same age. The same high estrogen levels that tend to protect women from atherosclerotic heart disease throughout premenopausal years seems to also stave off the ravages of osteoporosis; but when estrogen levels drop after menopause, the ability to maintain bone density drops dramatically as well, leaving susceptible women vulnerable to fractures that can be painful, debilitating, expensive, and even lethal. By age seventy-five, 90% of women are affected.
     Bone formation is a multi-faceted process involving calcium and Vitamin D in a delicate equilibrium; and beginning around the age of forty, the body begins having trouble utilizing and absorbing calcium and Vitamin D. Like other diseases that tend to affect older populations, the impact of osteoporosis escalates along with the average life expectancy of our population, becoming a significant health risk for women surviving other illnesses that have historically been more lethal. This situation is exacerbated by the recently publicized data indicating that the average woman’s diet, in large part due to avoidance of dairy products in pursuit of a “more healthy diet” from an atherosclerotic standpoint, has become progressively deficient in calcium intake over the past twenty years. Astoundingly, only 2% of the nation’s female population between the ages of fifteen and eighteen are currently consuming enough calcium to avoid osteoporosis later in life, so the problem is going to get much worse unless a profound change is effected.
     In spite of the fact that prognosis improves dramatically with such simple remedies as increased calcium intake and weight-bearing exercise, the problem continues to worsen on the whole due to widespread ignorance of the disease. Recent surveys indicate that most women not only fail to understand the risks associated with osteoporosis, but also misunderstand the nature of the disease, assuming that the appearance of warning signs will be ample notice to take remedial or preemptive steps. This view is based on the erroneous assumption held by MOST women that the warning signs of arthritis (swelling, tenderness, and stiffness of the joints) are actually the warning signs of osteoporosis.
     Unfortunately, this misconception couldn’t be further from the truth. The only warning sign most victims of osteoporosis get is a debilitating fracture, a sure indication that the disease has been progressing for years and has become a potentially lethal and irreversible condition. In contrast to arthritis, osteoporosis can currently only be detected by measuring bone density.

PATHOPHYSIOLOGY
     Just like most other organ systems, bones are constantly under construction; but unlike the skin, which simply sheds layers of dead cells and replaces them with dividing cells from below, the rigid infrastructure of bone must be perpetually torn down and rebuilt. Osteoclasts continually dissolve the rigid matrix, resorbing its components chemically to form resorption pits, which are then vacated and populated by osteoblasts that rebuild the matrix anew. Ideally in the adult, the net result is simply replacement of older, and perhaps damaged bone with new material in a new matrix of equal density – a perpetual renewal process.
     A number of conditions, though, can contribute to the progressive deterioration of density and quality of the new matrix. Obviously, if raw building materials for bone production (calcium and Vitamin D) are in short supply, the new bone produced will be of lower density.

DIAGNOSIS
     Definitive diagnosis is made by densitometry; but assessment of risk factors can point toward the majority of patients who need to be screened for lower bone density. Thin Caucasian or Asian women are the obvious largest target population, and of course a fracture is a definite reason to assess. Hypogonadism, whether via menopause or other impairment of estradiol production, is the other primary risk factor, with low calcium intake, smoking, high alcohol consumption, lack of exercise, high caffeine intake and glucocorticoid therapy as very significant contributory lifestyle factors.

TREATMENT
     Hormone Replacement Therapy (HRT), aimed at prolonging premenopausal estrogen levels, seems at first to be the ideal answer; and favorable results are indeed seen with such therapy. In addition to reducing the rate of bone loss, HRT reduces both incidence and severity of various untoward effects of menopause, like vaginal dryness, sleeplessness, incontinence, integumentary collagen loss, and hot flashes; and it seems to stave off the progression of atherosclerosis.
     Other long-term effects of HRT, though, tend to dissuade both clinicians and patients, with recent statistics indicating that the risk of breast cancer increases along with the improved prognoses for osteoporosis and atherosclerosis. Most women, faced with increased chances of breast cancer, will choose other alternatives for obvious reasons, regardless of the potential lethality of those other alternatives. The fact that “long-term” HRT is defined here as fifteen years or longer in duration, does little to soften the impact of such dire consequences. The “silent” progression of osteoporosis can hardly compete with the physical devastation and emotional/psychological impact of breast cancer. Controversy still reigns over this issue, and risks must be carefully evaluated in light of benefits.
     HRT can also pose a compliance problem, especially in the patient with an intact uterus, requiring progestins in addition to the estradiol. This combination therapy can significantly reduce the incidence of endometrial neoplasia or hyperplasia, but can cause it’s own unpleasant symptoms, like bloating, and unscheduled vaginal bleeding.
     Calcitonin (Calcimar, Miacalcin), normally produced by the thyroid’s parafollicular cells, inhibits the activity of the osteoclasts that break down the bone matrix; and this allows gradual build-up of bone mass with chronic therapy. The calcitonin from salmon (isolated in the ultimobranchial gland of fish and reptiles and inactivated by stomach secretions, so it can’t be acquired by eating the meat of such creatures) has some thirty times the activity of human calcitonin. Available in both injection and nasal spray, it should be reserved for women at least five years after menopause or for patients unable to tolerate or benefit from increased calcium intake.
     Bisphosphonates (Etidronate and Pamidronate) have been used with limited success for years for the treatment of Paget’s Disease; but long-term use necessary for osteoporosis is impractical because of side effects. With the advent of alendronate (Fosamax, though, osteoporosis therapy and prognosis has undergone tremendous change. It is important to understand that other measures, however successful in any given patient, can only slow the process of bone loss; so regardless of the effort expended on compliance, osteoporosis would never get any better and would remain a severe limitation on a patient’s lifestyle. Alendronate, an aminobiphosphonate, inhibits osteoclasts so effectively that a net gain in bone density can be realized in the average patient, so the bones actually become stronger.

Counseling the Osteoporosis Patient
     From a management standpoint, encouraging pharmacists to focus extra attention on the treatment of osteoporosis will not only enhance the professionalism of the retail pharmacy, but solidify patient loyalty for the astute pharmacist able to identify potential problems and stimulate OTC sales by careful recommendation of calcium and Vitamin D supplements. Pharmacists should become very familiar with the various OTC products and should be encouraged to spend extra time, not only with patients actively treated for osteoporosis, but with patients the pharmacist is able to identify as at risk for the disease.
      Prevention is the best policy, and preventive measures are appropriate for women of any age. Women should be apprised of their basic need for calcium and Vitamin D supplementation with emphasis on the new recommendations for daily intake. Smoking and drinking tend to increase one’s chances of incurring problems with osteoporosis, while exercise tends to reduce those chances. Ensuring adequate calcium and Vitamin D intake remains equally important for patients treated with hormone replacement therapy, calcitonin, or alendronate.
     Patients at particular risk are identified as Asian or Caucasian of slender build, especially those over the age of forty; and certain medications can also increase the need for supplementation. Corticosteroids reduce calcium absorption from the GI tract, so long-term use of such medications by any route (even via inhalers) will predispose the patient to bone density loss. Similarly, phenytoin can interfere with absorption of Vitamin D to generate the same result, and calcium levels can be adversely affected by thyroid supplementation, furosemide, and antacids containing aluminum.

     Patients prescribed Miacalcin Nasal Spray should be directed to the patient package insert, which details the necessary information; but the pharmacist should be well-informed and prepared to answer common questions. Once dispensed and assembled, the product can be stored at room temperature (not in the car in July – it’s a heat-labile protein) for up to four weeks; but with daily use, alternating nostrils daily to minimize rhinitis, the supply should only last two weeks.
     Each new pump assembly must be “activated” or primed by squirting about six times until a faint spray is seen before actual administration to a nostril. This ensures accurate dose measurement by the device, and the loss of this tiny amount of medication in the priming process is anticipated by the manufacturer with a slight overfill. It is unnecessary to inhale the spray, as the medication is absorbed through the nasal mucosa.

     Patients prescribed Fosamax should be well-versed on its proper use. The daily dose must be taken with a full glass of water (not mineral water) the first thing in the morning at least thirty minutes (and optimally two hours) before eating or drinking anything but that glass of water. The presence of anything else (even juice, coffee, or other medications – including calcium supplements) in the stomach reduces the absorption of alendronate dramatically.
     Since esophageal irritation is a common side effect of alendronate, the patient should be specifically warned not to wake up early, take her Fosamax, then go back to bed for the prescribed thirty minutes to two hours. It is important for her to remain upright for that period to facilitate dissolution and absorption in the stomach and to prevent esophageal irritation. Concurrent therapy with aspirin or any NSAID compounds the likelihood of esophageal ulceration and will require close monitoring.
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