From: Subject: Pharmacy Times CE: Osteoporosis: "Need-to-Knows" for Pharmacists About Bone Health Date: Tue, 6 Oct 2009 14:26:10 +0300 MIME-Version: 1.0 Content-Type: multipart/related; type="text/html"; boundary="----=_NextPart_000_0000_01CA4690.F366B570" X-MimeOLE: Produced By Microsoft MimeOLE V6.00.2900.5579 This is a multi-part message in MIME format. ------=_NextPart_000_0000_01CA4690.F366B570 Content-Type: text/html; charset="windows-1256" Content-Transfer-Encoding: quoted-printable Content-Location: file://C:\Documents and Settings\maisa.JPA\Local Settings\Temporary Internet Files\Content.IE5\WTAMOFHB\200906-01.htm Pharmacy Times CE: Osteoporosis: "Need-to-Knows" = for Pharmacists About Bone Health

ACPE Program I.D.=20 Number:
290-000-09-009-H01-P

Pharmacy Times Office of Continuing Professional = Education=20 is accredited by the Accreditation Council for Pharmacy = Education as=20 a provider of continuing pharmacy education. This program = is=20 acceptable for 1.5 hours of Continuing Education Credits = (0.15 CEU)=20 through 6/1/2012.

Osteoporosis: "Need-to-Knows" for Pharmacists About Bone Health

Joanne LaFleur , PharmD, MSPH

Educational Objectives

After participating in this activity, = participants=20 should be better able to:

  1. Describe the incidence, prevalence, and burden for osteoporosis.
  2. Explain the pathophysiologic and metabolic basis for low bone = density and=20 osteoporosis.
  3. Identify and recognize risk factors for development of = osteoporosis, and=20 perform risk assessment for patients based on osteoporosis risk = factors.
  4. Discuss the current treatment options for patients diagnosed with=20 osteoporosis, their place in therapy and limitations, as well as = options for=20 patients at risk for development of osteoporosis.
  5. Counsel patients about interventions for the prevention and = management of=20 osteoporosis, focusing on medication compliance and dietary and = lifestyle=20 modifications.
  6. Provide education to patients about medications to use for the = treatment=20 of osteoporosis, focusing on the importance of adherence.

Osteoporosis, which means "porous bone," is the most common bone = disease=20 among adults in the United States. It is defined as a disease in which = bone=20 tissue mass and architecture deteriorate, leading to bone fragility and = an=20 increased risk for fracture. Osteoporosis fractures occur most = frequently at the=20 hip, spine, or wrist, but osteoporosis can affect any bone.

In the United States today, 44 million people have osteoporosis. This = represents more than half of all adults aged 50 and older. Another 34 = million=20 have osteopenia, a precursor of osteoporosis in which bones are = weakened. The=20 risk of osteoporosis is higher in women than in men and in Asians and = Caucasians=20 than in Hispanics and blacks. It is estimated that >2 million = fractures=20 currently occur annually in the United States. This number is expected = to=20 increase as the population ages. The direct costs of osteoporosis = increase every=20 year and are anticipated to reach $50 billion by 2040.1

Pathophysiology

All our lives, our bones are constantly undergoing 2 processes: = formation=20 (forming new bone), which is done by specialized cells called = osteoblasts, and=20 resorption (breaking down old bone), which is done by = osteoclasts.2=20 During youth and adolescence, the rate of bone formation exceeds the = rate of=20 resorption, so our bones grow and increase in density. In our 20s, bones = usually=20 reach their peak mass, and new bone formation begins to slow.

The balance between bone formation and resorption continues in = equilibrium=20 throughout much of our lives, keeping bones strong. At about midlife, = the rate=20 of bone resorption begins to overtake the rate of bone formation in both = men and=20 women, and net bone loss begins to occur. In women, the imbalance = between=20 formation and resorption accelerates at menopause when estrogen levels = drop,=20 causing more rapid bone loss. As much as 20% of a woman's bone mass can = be lost=20 in the first 5 to 7 years after menopause.3

Osteoporosis can be classified as either primary or secondary. = Primary=20 osteoporosis, which occurs later in life, is categorized as either type = 1=20 (postmenopausal osteoporosis) or type 2 (senile osteoporosis). Secondary = osteoporosis is characterized by bone loss caused by other conditions or = exposures (Table 1) and can occur in susceptible patients at any = age.

Type 1 generally develops in women after menopause when estrogen = levels=20 decline. It occurs in 5% to 20% of women, usually within a few years of = the=20 onset of menopause. Type 1 accounts for the significantly greater risk = for=20 osteoporosis in women than in men.

Type 2 osteoporosis typically happens in the very elderly = (>70=20 years), and occurs twice as frequently in women as in men. Type 2 occurs = when=20 the balance between resorption and formation is lost, and the rate of = bone=20 breakdown exceeds that of bone building. Type 2 may be exacerbated by=20 age-related reduction in vitamin D synthesis or reduced vitamin D = activity. In=20 older women, types 1 and 2 frequently occur together. All types of = osteoporosis=20 are treated the same way, but in the case of secondary osteoporosis, = underlying=20 causes also should be identified and treated.

3D"Table
Table=20 1

Secondary osteoporosis is caused by many conditions and exposures, = but=20 pharmacists should be aware of the medications that lead to bone loss, = listed in=20 Table 1. The most predominant of these is glucocorticoid use, which is=20 considered a clinical risk factor for fracture under the most recent=20 guideline.1 The level of exposure considered to be a risk = factor is=20 the equivalent of at least 5 mg prednisolone daily for at least 3 = months, which=20 is equivalent to the following average daily exposures of other=20 glucocorticoids:

Epidemiology

The technical definition of osteoporosis is a bone mineral = density=20 (BMD) level >2.5 standard deviations below the young adult reference = mean.=20 Patients with BMDs below this level and who have had a fracture meet the = definition of established or severe osteoporosis. The=20 prevalence of osteoporosis depends on which site is measured for BMD. In = the=20 United States, 17% of postmenopausal Caucasian women had osteoporosis of = the hip=20 (12% for Hispanics and 8% for blacks).5 When other bone sites = also=20 are considered, including the spine and forearm, the prevalence = increases to=20 33%.6 Prevalence also increases with age. Among patients aged = 50 to=20 59, the prevalence of osteoporosis at the hip and at any site is 4% and = 15%,=20 respectively. These figures increase to 48% and 70% after the age of=20 80.5

Risk Factors

Decreased BMD is the primary clinical measure for osteoporosis and = the most=20 predominant indicator. BMD is usually expressed as a T-score, = which is=20 defined as the number of standard deviations from the mean BMD for young = adults.=20 Although T-scores are the most common metric used, sometimes a Z-score = is=20 reported. A Z-score is defined as the number of standard = deviations=20 from the mean BMD for age- and sex-matched patients. A BMD Z-score of = less than=20 -1.5 is usually an indicator that factors other than aging are = contributing to=20 bone loss. A T-score between -1 and -2.5 is the definition of = osteopenia,=20 whereas a T-score of -2.5 or lower is the definition of osteoporosis. = T-scores=20 are the most common metric used and serve as the basis for treatment=20 recommendations.

Until recently, BMD also was the main risk factor for fracture = considered in=20 risk assessment; treatment initiation was recommended in women (men were = not=20 included) whose BMD T-scores (the number of standard deviations from the = mean=20 BMD for young adults) were less than -2.5.7-9 Over time, = however,=20 researchers discovered that more than half of fragility fractures = occurred in=20 patients whose BMD T-scores were above the diagnostic threshold for=20 osteoporosis.10 That finding resulted in a large body of = osteoporosis=20 risk factor research. It is now known that bone density is only 1 of = many risk=20 factors to consider. The important risk factors for osteoporosis and = fracture=20 are summarized below.11

Alcohol Use
High levels of alcohol use = are known=20 to cause bone loss. The mechanism is not known, but it may occur through = changes=20 in protein and calcium metabolism, decreased mobility, decreased gonadal = function, or even a direct toxic effect on osteoblasts. Moderate alcohol = use is=20 not known to affect bone density or fracture risk.

Body Mass Index
Low body mass index = (BMI) is=20 known to correlate with low peak bone mass, as well as increased hip and = vertebral fracture risk. It is thought that this may be caused by lower = adipose=20 estrogen and less mechanical loading on the skeleton. The threshold for = risk is=20 a BMI of <19 kg/m2.

Bone Density
Low bone density is common = in older=20 patients, smokers, those with a high caffeine intake, patients with = prior=20 gastric surgery, or a maternal history of fracture. Some factors = associated with=20 higher bone density are older age at menopause, estrogen or thiazide = use, type 2=20 diabetes, greater height and/or weight, good muscle strength, and high = calcium=20 intake.

Cigarette Smoking
Cigarette smoking = reduces BMD,=20 possibly by contributing to an earlier menopause, reducing body weight, = and=20 enhancing the metabolism of exogenous estrogen in women. Many studies = have=20 linked smoking with a decreased peak bone mass.

Falls
Falls are one of the most common = causes of=20 osteoporotic fractures. About half of falls occur in the presence of=20 environmental hazards, such as slippery floors, unstable furniture, and = poor=20 lighting. Another 50% occur in the presence of common age-related = conditions,=20 such as gait instability, muscle weakness, decreased reflexes, and poor = vision.=20 Chronic illness (neurologic disorders, heart disease, stroke, urinary=20 incontinence, depression, and impaired cognition) also may contribute to = falls,=20 as will some medications (hypnotics, antidepressants, and sedatives). = The risk=20 increases with age and the number of comordid conditions. About 5% of = falls=20 result in a fracture. In addition, a prior osteoporotic fracture = increases the=20 risk of future fractures in both men and women.

Genetics
Family history is an important = risk=20 factor. About half of the variance in peak bone mass is explained by = genetics,=20 as are much of the variances in bone architecture and strength. A family = history=20 of hip fracture is an important clinical risk factor for fracture.

Hypogonadism
Primary hypogonadism is = associated=20 with low bone density in both sexes. A decrease in estrogen production = at=20 menopause is the most important contributing factor to osteoporosis. = Secondary=20 amenorrhea, as the result of anorexia nervosa, excessive exercise, or = chronic=20 disease, also increases the risk for osteoporosis. Premature = menopause,=20 defined as occurring at an age <45 years (including surgically = induced=20 menopause), is a strong risk factor for osteoporosis and fracture.

Nutrition
Dietary factors are important=20 determinants of peak bone mass and agerelated bone loss. Calcium and = vitamin D=20 deficiencies are easy to detect and correct. Dietary calcium intake is = known to=20 increase BMD and decrease hip fracture risk.12 Vitamin D = deficiency=20 increases parathyroid hormone production, which increases bone turnover = and bone=20 loss. Low levels of vitamin D are common in the elderly. Some potential=20 explanations for this include decreased efficiency in converting = sunlight to=20 vitamin D, decreased sun exposure in the elderly, and decreased = absorption.=20 Supplementing the diet with vitamin D strengthens bones and improves = muscle=20 strength, which reduces both the risk and consequences of falling. Other = nutritional considerations for maintaining bone health are maintaining = an=20 adequate protein intake, limiting phosphate (particularly in the = presence of low=20 calcium), and maintaining adequate vitamin K and magnesium intake.

Physical Inactivity
Immobility has a = detrimental=20 effect on bone mass. Some chronic diseases that decrease mobility are = associated=20 with low bone mass. Bone density increases in response to weight-bearing = exercise; high-impact exercises are more beneficial to bone density than = low-impact ones.

Screening and Guidelines

In the past, BMD screening was the principal method for identifying = patients=20 with osteoporosis who would benefit from treatment. The sensitivity of = BMD=20 measurements is limited, however; more than half of patients who will = fracture=20 have BMD scores above the threshold for osteoporosis. This has led to a = growing=20 body of research demonstrating how fracture risk assessment can be = improved by=20 ascertaining additional risk factors.

In 2008, the National Osteoporosis Foundation (NOF) published a new = guideline=20 for the identification and treatment of osteoporosis and osteoporosis=20 fractures.1 The guideline relies on the use of an online = tool, called=20 the FRAX, which estimates patients' absolute risks for hip fracture or = any major=20 osteoporotic fracture.13 Risk factors used in the FRAX = assessment=20 include race, age, sex, prior fracture history, family history of hip = fracture,=20 smoking status, glucocorticoid exposure, medical history of rheumatoid=20 arthritis, secondary osteoporosis, alcohol use, BMD, and BMI (if BMD is = not=20 known). The new NOF guideline recommends treatment in men and women = whose=20 absolute 10-year risk for any major osteoporotic fracture or hip = fracture is 20%=20 or 3%, respectively.1 These thresholds are based on = US-specific=20 cost-effectiveness analysis in which a generic bisphosphonate was = used.

The idea of using risk assessment tools that calculate patients' = absolute=20 risks of adverse disease outcomes is not new, nor is it limited to = osteoporosis.=20 Many clinicians are familiar with the Framingham risk calculator that = guides=20 treatment decisions for cardiovascular disease prevention. The FRAX is a = similar=20 tool for osteoporosis. One advantage to the FRAX is that a score can be=20 calculated without knowing the patient's BMD; instead, the tool uses = BMI, which=20 has been shown in studies to approximate the risk of fracture associated = with=20 low bone mass.

A recent study reported that FRAX scores calculated with and without = BMD=20 would result in the same treatment decision about 90% of the time in=20 postmenopausal women.14 FRAX scores calculated without BMD = are most=20 likely to be inaccurate in elderly patients with normal bone mass or in = young=20 patients with high BMI; in these patient subsets, clinicians may want to = rely=20 more heavily on BMD to accurately estimate fracture risk.

Pharmacologic Therapy

Many agents have proven beneficial for preventing hip, vertebral, and = nonvertebral fractures in postmenopausal women, including alendronate,=20 risedronate, zoledronic acid, and estrogen.15 Other available = agents,=20 including the selective estrogen receptor modulator (SERM) raloxifene, = the=20 bisphosphonate ibandronate, and the anabolic agent teriparatide, have = been shown=20 to decrease risk of vertebral fractures only.15,16 The agents = that=20 are approved by the FDA to treat or prevent osteoporosis in = postmenopausal women=20 include 4 bisphosphonates, as well as raloxifene, teriparatide, = estrogen, and=20 calcitonin.

Bisphosphonates
Bisphosphonates are = usually=20 considered first-line therapy for the treatment or prevention of = osteoporosis.=20 The 4 bisphosphonates approved by the FDA for this purpose are = alendronate,=20 risedronate, ibandronate, and zoledronic acid. Of the 4, alendronate has = been on=20 the market the longest and is the only bisphosphonate currently = available as a=20 generic. Other bisphosphonates (etidronate and pamidronate) are not = approved for=20 osteoporosis and should not be recommended.

Table 2 summarizes the dosage forms and dosing frequencies available = for each=20 bisphosphonate. Most of the bisphosphonates, except for zoledronic acid, = come in=20 oral formulations that can be dosed at frequencies ranging from daily to = monthly. The oral bisphosphonates are not absorbed very well (<1%), = so it is=20 critical that patients take them on an empty stomach with a full glass = of water=20 and avoid eating for at least 60 minutes after administration to = maximize=20 absorption. The oral bisphosphonates also cause gastric irritiation, so = patients=20 should not lie down for at least 60 minutes in order to avoid esophageal = erosion.


3D"Table
Table=20 2

Ibandronate and zoledronic acid are available in longer-acting = intravenous=20 (IV) formulations. IV formulations are 100% absorbed, dosed less = frequently, and=20 patients do not have to adhere to difficult and unpleasant = administration=20 restrictions. Ibandronate IV can be administered quarterly and = zoledronic acid=20 yearly. Ibandronate should be administered over 15 to 30 seconds and = zoledronic=20 acid over no less than 15 minutes in order to avoid serious renal = toxicity. The=20 difference in these infusion times means that ibandronate can be = administered=20 quickly in the physician's office every 3 months, whereas zoledronic = acid=20 usually requires a yearly visit to an infusion center. Neither infusion = should=20 be administered to patients with severe renal impairment (creatinine = clearance=20 <30 mL/minute for ibandronate and <35 mL/minute for zoledronic = acid).=20 Before receiving either infusion, patients should be wellhydrated, and = their=20 serum creatinine always should be checked.

Sidebar 1

Osteonecrosis of the=20 Jaw
Patients and health care professionals have given a = great=20 deal of attention to the risk of osteonecrosis of the jaw (ONJ) = occurring=20 in patients who receive bisphosphonates. ONJ is characterized by = pain,=20 swelling, exposed bone, infection, or fracture of the jawbones and = usually=20 occurs as a result of incomplete healing following a dental = procedure.=20 Although most cases have been in patients with cancer who received = high-dose intraveneous (IV) bisphosphonates, rare cases have been = reported=20 in postmenopausal osteoporosis patients taking oral=20 bisphosphonates.41,42 The risk of ONJ in osteoporosis = therapy=20 is very low, about 1 in 10,000 to 100,000.43-45

Osteoporosis experts recommend that pharmacists talk about the = risk of=20 ONJ along with signs, symptoms, and risk factors in patients newly = starting oral bisphosphonates.43,46 These risk factors = include=20 the following:

  • Cancer or anticancer therapy
  • Dental extractions or implants
  • Glucocorticoid use
  • IV bisphosphonates
  • Long duration of bisphosphonate use
  • Poorly fitting dentures
  • Preexisting dental disease
  • Smoking

It is not necessary for patients to visit the dentist before = beginning=20 treatment, but patients should be counseled to practice good oral = hygiene=20 and visit a dentist regularly while on therapy. Because the risk = of ONJ is=20 associated with dental procedures, dental experts have provided a=20 consensus guideline for dentists and oral surgeons who treat = patients who=20 take bisphosphonates.47 The guideline states that = dental=20 surgeries, extractions, and implants can be performed without = extra=20 safeguards in patients who have received oral bisphosphonates for = <3=20 years.47 In patients who have been treated >3 years, = they=20 recommend discontinuing the oral bisphosphonate for 3 months = before=20 performing the procedure and restarting therapy after the bone has = healed.=20 This recommendation is not supported by any evidence that it will = decrease=20 the risk of ONJ. In fact, the long half-life and duration of = action of=20 bisphosphonates suggests that it is unlikely to make a difference. = Osteoporosis experts believe, however, that short-term = discontinuation=20 surrounding dental procedures is not likely to hurt patients' BMD = levels=20 or fracture risk.43

Raloxifene
Raloxifene is the only SERM = that is=20 FDA-approved to treat or prevent osteoporosis in postmenopausal women. = Another=20 SERM, tamoxifen, is only approved for cancer treatment or prevention, = but it may=20 have some beneficial effects on the bone. Raloxifene improves bone mass = and=20 prevents vertebral fractures.17,18 Raloxifene is not as = effective as=20 the bisphosphonates and should not be used as first-line therapy unless = the=20 patient cannot tolerate bisphosphonates or is concerned about breast = cancer=20 risk. It is dosed at 60 mg/day and taken without dietary = restrictions.

Teriparatide
Teriparatide, a form of = parathyroid=20 hormone, is considered an anabolic osteoporosis treatment, as opposed to = the=20 antiresorptive bisphosphonates and SERMs. Anabolic agents stimulate bone = formation and remodeling; antiresorptives suppress bone resorption. = Because of=20 their different mechanisms of action, it has been hypothesized that = using both=20 anabolic agents and antiresorptives concomitantly may lead to greater = gains, but=20 this has not been shown to be the case.

Product labeling for teriparatide contains a black box warning for=20 osteosarcoma, which is the most worrisome adverse event associated with=20 teriparatide use. Of more than 300,000 patients exposed to teriparatide=20 worldwide, 1 case of osteosarcoma has been reported. Although causality = could=20 not be established, the FDA does not recommend use of teriparatide in = patients=20 who may already have an increased risk of osteosarcoma, such as patients = with=20 Paget's disease, elevated alkaline phosphatase, and other factors.

In clinical trials, monotherapy with teriparatide at both 20 mcg/day = and 40=20 mcg/day reduced vertebral and nonvertebral fractures at the same = magnitude,=20 although the higher dose also resulted in greater increases in = BMD.16=20 Combination therapy of teriparatide plus alendronate did not result in = any=20 additional BMD benefits, compared with teriparatide alone.19 = It is=20 possible, however, that greater fracture reduction efficacy may be = realized when=20 they are administered sequentially-1 year of parathyroid hormone = followed by=20 antiresorptive therapy.20 Teriparatide is dosed at 20 = mcg/day,=20 administered as a subcutaneous injection.

Estrogen
Because of the significant = risks for=20 breast cancer, stroke, venous thromboembolism, and coronary disease, = estrogen=20 and estrogen/progestin are no longer considered to be first-line = treatment for=20 osteoporosis,21 although they may be used in postmenopausal = women if=20 they have persistent menopausal symptoms or if they cannot tolerate = first-line=20 drugs. Both unopposed estrogen and estrogen with progestin are highly = effective=20 at preventing hip and vertebral fractures.21

Calcitonin
Calcitonin is a peptide that = binds to=20 osteoclasts and inhibits bone resorption. Calcitonin is usually dosed as = 200=20 international units (IU) intranasally daily. In at least 1 clinical = trial, 5=20 years of calcitonin was associated with a small reduction in vertebral = fracture=20 risk.22 Evidence from head-tohead studies suggests that the = efficacy=20 of calcitonin is much lower than that of alendronate, = however.23=20 Calcitonin may have some beneficial effects on bone pain, suggesting = that it may=20 be a choice in patients with pain from an acute fracture.24=20 Calcitonin is usually dosed as 200 IU (1 spray) intranasally per day,=20 alternating nostrils daily. Calcitonin also may be administered as = subcutaneous=20 or intramuscular injection at a dose of 100 IU every other day.

Adverse Effects of Pharmacotherapy

Like all medications, osteoporosis treatments come with adverse = effects.=20 Muscle pain and some other important adverse effects of osteoporosis = agents are=20 summarized in Table 3.15,16,25-40 With bisphosphonates, the = most=20 important ones to discuss with patients are osteonecrosis of the jaw = (ONJ) and=20 muscle pain. ONJ is discussed in depth in Sidebar = 1.41-47

3D"Table
Table=20 3

Nonpharmacologic Therapy

Calcium/Vitamin D
Adequate intake of = calcium and=20 vitamin D are important to maintain bone health. Vitamin D enhances = intestinal=20 calcium absorption. Although a number of clinical trials have shown that = calcium=20 and vitamin D increase BMD, the evidence does not support efficacy for = fracture=20 prevention. This may be due to poor compliance; in 1 study, a subgroup = analysis=20 showed that vitamin D supplementation decreased fracture risk in = compliant=20 patients.48

Despite the mixed evidence on efficacy, most guidelines suggest that = a=20 postmenopausal woman's total calcium intake should include 1500 mg/day = of=20 calcium, of which 500 to 1000 mg/day can be in the form of calcium=20 supplements.49 Calcium supplements, which are available in = several=20 salts (calcium carbonate and calcium citrate are the most common), = should be=20 taken at mealtimes to maximize absorption. Calcium supplements greater = than 500=20 mg should be taken in divided doses since the body can only absorb 500 = mg of=20 elemental calcium at a time. Women also should get a minimum of 800 = IU/day of=20 vitamin D, more if they have an absorption disorder or if they are = receiving=20 anticonvulsants that increase vitamin D metabolism.

Sidebar 2

Osteoporosis = in=20 Men
Most people consider osteoporosis to be a disease = that=20 occurs in women, but men are also at high risk. In fact, 1 of = every 4 men=20 who lives to age 60 will have a fragility fracture in his = remaining=20 lifetime.63 Although it occurs less frequently than in = women,=20 osteoporosis in men is often more serious. Compared with women, a = man who=20 breaks his hip is twice as likely to die in the next = year.64=20 The importance of knowing how to evaluate osteoporosis risk in men = will=20 continue to increase as the population ages.

Until recently, guidelines for osteoporosis screening did not = even=20 contain recommendations for men.7-9 In part, this might = be=20 because screening consisted of only measuring bone mineral density = (BMD),=20 which has limited sensitivity in women and performs even worse in = men.=20 Only 1 in 5 men who will have a serious fracture can be identified = on the=20 basis of BMD (the number in women is closer to half).65 = The=20 most recent guideline from the National Osteoporosis Foundation, = which=20 recommends using the FRAX and consideration of other non-BMD risk = factors,=20 expands recommendations for screening and treatment to also = include=20 men.1

Many of the same agents used to treat osteoporosis in women = also can be=20 used in men. Alendronate, risedronate, and zoledronic acid are all = approved by the FDA to prevent or treat osteoporosis in men, and=20 bisphosphonates are considered the first-line treatment. = Teriparatide=20 should be reserved for men who do not improve with bisphosphonates = or who=20 have severe disease. Testosterone, often considered a treatment = option for=20 men, increases bone density in men with low = testosterone,66-68=20 but does not in otherwise healthy men.69 Testosterone = has never=20 been shown to reduce fractures.15 It should not be used = to=20 treat osteoporosis in men unless they also have=20 hypogonadism.

The best way to get calcium and vitamin D is through diet. For = calcium, dairy=20 products are the best natural source, with each 8-oz serving of milk, = yogurt,=20 ice cream, or cottage cheese providing about 300 mg of calcium. Each = 1-oz=20 serving of hard cheese provides about 300 mg. Many other foods, such as = dark=20 green vegetables, nuts, breads, and cereals, also supply an average of = 100 mg of=20 calcium per serving. If dietary intake is below the recommendation, = calcium=20 supplements should be recommended. For vitamin D, fortified milk is the = largest=20 source, containing about 100 IU per 8-oz serving. Sunlight exposure also = increases vitamin D, but it is not a reliable source because sunscreen = products=20 block vitamin D synthesis and because elderly patients-those most at = risk for=20 osteoporosis-do not convert vitamin D as efficiently as younger = patients.=20 Vitamin D also is available as a dietary supplement.

Exercise
Exercise improves bone density = and=20 decreases fracture risk in older women.50,51 That is why = pharmacists=20 should recommend exercise for both treatment and prevention of = osteoporosis. The=20 minimum recommendation is 30 minutes of weight-bearing exercise, such as = walking, aerobics, and weight training, at least 3 times per week. The = benefits=20 of exercise for preventing fractures are realized via 2 main mechanisms. = Exercise increases bone density and makes bones stronger,52 = and it=20 also improves muscle strength, decreasing fall risk.50,53

Smoking cessation Smoking cessation should be recommended to all = women, but=20 particularly among women seeking to treat or prevent osteoporosis = because=20 smoking decreases bone density.54 In patients who are = receiving=20 estrogen supplementation, smoking also can decrease the beneficial = effects of=20 estrogen on bones.55,56

Adherence to Pharmacotherapy

It goes without saying that the benefits of pharmacotherapy cannot be = realized if patients do not take their medications, and evidence shows = that=20 better patient adherence and persistence is associated with reduced = fracture=20 risk.57 Patient adherence and persistence with = bisphosphonates has=20 been reported to be very low in most studies, however. In 1 study, less = than an=20 average of 25% of doses were taken by patients at 1 year,58 = in=20 another, nearly half of patients stopped taking bisphosphonates, before = 1=20 year,59 and in a third, 70% of patients failed to take at = least 80%=20 of their doses by 1 year.60 Some evidence indicates that = patients=20 demonstrate better adherence with bisphosphonates, compared with other=20 treatments,60-62 but overall, adherence and persistence are = poor with=20 all osteoporosis treatments.

With the bisphosphonates, a likely reason for poor adherence is the=20 gastrointestinal adverse effect profile and the administration = restrictions on=20 food and position. It has been hypothesized that the less frequent = dosing of the=20 newer bisphosphonates may improve adherence, but no studies have been = able to=20 document substantial improvements in adherence with the monthly or = quarterly=20 dosing, compared with daily or weekly. For this reason, the quarterly or = yearly=20 infusions may be a good choice in patients who fail to adhere to oral=20 regimens.

Conclusion

Whereas osteoporosis is a serious and prevalent bone disease in=20 postmenopausal women, men also are at high risk (Sidebar 2). Pharmacists = should=20 be aware of risk factors for osteoporosis and should be able to estimate = a=20 patient's 10-year absolute risk for fracture. Pharmacists also should be = able to=20 make treatment recommendations. Antiresorptives are considered = first-line=20 treatment for osteoporosis. Specificially, bisphosphonates should be=20 recommended, except in patients who cannot tolerate them. Raloxifene, = another=20 first-line treatment, should be used in patients who fail = bisphosphonates or who=20 have a high risk for breast cancer. Teriparatide, an effective anabolic = agent,=20 should be reserved for patients with severe disease. Calcitonin is = useful in=20 patients with acute, painful fractures. Estrogen should not be used for=20 osteoporosis prevention. Patient adherence to osteoporosis medications = continues=20 to be poor, but newer agents may have potential for better = adherence.

References

  1. National Osteoporosis Foundation. Clinician's Guide to Prevention = and=20 Treatment of Osteoporosis. 2008. www.no= f.org/professionals/NOF_Clinicians_Guide.pdf.=20 Accessed April 18, 2009.
  2. US Department of Health and Human Services Office of the Surgeon = General.=20 Bone Health and Osteoporosis: A Report of the Surgeon General. ww= w.surgeongeneral.gov/library/bonehealth/content.html.=20 Accessed March 28, 2009.
  3. National Osteoporosis Foundation. Osteoporosis Bone Basics. www.nof.org/osteo= porosis/bonehealth.htm.=20 Accessed March 28, 2009.
  4. Templeton K. Secondary osteoporosis. J Am Acad Orthop Surg.=20 2005;13(7):475-486.
  5. Looker AC, Orwoll ES, Johnstone CC Jr, et al. Prevalence of low = femoral=20 bone density in older US adults from NHANES III. J Bone Miner = Res.=20 1997;12(11):1761-1768.
  6. Melton LJ 3rd, Atkinson EJ, O'Connor MK, O'Fallon WM, Riggs BL. = Bone=20 density and fracture risk in men. J Bone Miner Res.=20 1998;13(12):1915-1923.
  7. US Preventive Services Task Force. Screening for Osteoporosis in=20 Postmenopausal Women. Rockville, MD: Agency for Healthcare Quality and = Research; 2002. ww= w.ahrq.gov/clinic/3rduspstf/osteoporosis/osteorr.htm.=20 Accessed May 4, 2009.
  8. National Osteoporosis Foundation. Physician's Guide to Prevention = and=20 Treatment of Osteoporosis. Washington, DC: National Osteoporosis = Foundation;=20 2003.
  9. Hodgson SF, Watts NB, Bilezikian JP, et al. American Association = of=20 Clinical Endocrinologists medical guidelines for clinical practice for = the=20 prevention and treatment of postmenopausal osteoporosis: 2001 edition, = with=20 selected updates for 2003. Endocr Pract. 2003;9(6):544-564.
  10. Siris ES, Chen YT, Abbott TA, et al. Bone mineral density = thresholds for=20 pharmacological intervention to prevent fractures. Arch Intern = Med.=20 2004;164(10):1108-1112.
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Joanne LaFleur, PharmD, MSPH, is Research Assistant Professor, = University=20 of Utah College of Pharmacy, Salt Lake City, Utah. Dr. LaFleur discloses = that=20 she has received research support from Novartis Pharmaceuticals and has = served=20 on a speaker's bureau for Roche


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