Vignettes in Osteoporosis: A Road Map to Successful Therapeutics

Authors

  • Clifford J Rosen,

    Corresponding author
    1. Maine Center for Osteoporosis Research and Education, St. Joseph Hospital, Bangor, Maine, USA
    • Address reprint requests to: Clifford J Rosen, MD St. Joseph Hospital Maine Center for Osteoporosis Research and Education 900 Broadway, Bldg #2 Bangor, ME 04401, USA
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  • Dennis M Black,

    1. Prevention Sciences Group, University of California at San Francisco, San Francisco, California, USA
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  • Susan L Greenspan

    1. Osteoporosis Prevention and Treatment Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
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  • Dr Black serves as a consultant for Merck & Co., Inc., Novartis, and NPS Pharmaceuticals. In addition, he has received funding from the aforementioned companies. Dr Greenspan serves as a consultant for Eli Lilly and Company and Merck & Co., Inc. She has received grant money from Eli Lilly and Company, Merck & Co., Inc., and Procter & Gamble. Dr Rosen has received grants from Eli Lilly and Company, Merck & Co., Inc., and Novartis.

Abstract

The diagnosis and management of osteoporosis have become increasingly more complex as new drugs enter the marketplace and meta-analyses of randomized trials with “other” agents become more prolific. We describe five common clinical scenarios encountered in the practice of osteoporosis medicine and various road maps that could lead to successful therapy.

Introduction: The diagnosis and treatment of osteoporosis have changed dramatically in the last decade. Advances in diagnostic technologies and a range of newer treatment options have provided the clinician with a wide array of choices for treating this chronic disease. Despite the issuance of several “guidelines” and practice recommendations, there still remains confusion among clinicians about basic approaches to the management of osteoporosis. This paper should be used as a case-based approach to define optimal therapeutic choices.

Materials and Methods: Five representative cases were selected from two very large clinical practices (Bangor, ME; Pittsburgh, PA). Diagnostic modalities and treatment options used in these cases were selected on an evidence-based analysis of respective clinical trials. Subsequent to narrative choices by two metabolic bone disease specialists (SG and CR), calculation of future fracture risk and selection of potential alternative therapeutic regimens were reviewed and critiqued by an epidemiologist (DB).

Results: A narrative about each case and possible management choices for each of the five cases are presented with references to justify selection of the various therapeutic options. Alternatives are considered and discussed based on literature and references through July 2003. The disposition of the individual patient is noted at the end of each case.

Conclusions: A case-based approach to the management of osteoporosis provides a useful interface between guidelines, evidence-based meta-analyses, and clinical practice dilemmas.

INTRODUCTION

Osteoporosis is a common disorder, especially among older postmenopausal women. It is characterized by skeletal fragility, reduced bone mineral density (BMD), and significant morbidity. Not surprisingly, the impact of this disease on society from an economic, medical, and social perspective is immense. In the last decade, important strides have been made in both the diagnosis and treatment of osteoporosis. Clinicians now have the capability to accurately estimate fracture risk “at the bedside” and define the relative efficacy of various therapies. As a result, the use of antiresorptive agents has grown exponentially and is firmly established among providers and patients. We are also now beginning to see the emergence of anabolic therapies. In a rapidly changing medical environment, the clinician is not only faced with a choice of who and when to treat, but what therapy to use and for how long. As such, the “art” of treating osteoporosis has become anything but routine. While publications of guidelines and therapeutic recommendations have clarified clinical decision-making for some patients, there are many cases in which clinical dilemmas remain.(1) Therefore, we believe some case-based examples founded on evidence from randomized clinical trials will provide an opportunity for the reader to relate problem solving in specific clinical situations to his/her practice. However, a word of caution: there is no “gold standard” for treating patients with osteoporosis; this paper should be considered a reference point to begin discussions with patients about their future goals and the role of various therapeutic options on the course of their disease.

CASE 1: LOW BMD IN AN EARLY POSTMENOPAUSAL WOMAN

LR is a 52-year-old newly menopausal white woman. She has hot flashes, but has suffered no fractures and no height loss. She is of average height and weight (5′2” [157 cm]; 135 lbs [61 kg]) for her age. She has an intact uterus. There is no family history of osteoporosis, and she had never undergone bone density testing. However, recently her primary care provider ordered a BMD test that revealed a lumbar spine T-score of −1.8 and a femoral neck T-score of −1.5. She presents now for a discussion about her “osteopenia” and what possible treatment options are available for her.

This is a very common clinical scenario for various reasons, not the least of which is the introduction of direct-to-consumer advertising “to know your T-score,” as well as major osteoporosis awareness campaigns by industry and advocacy groups. This woman, rightly or wrongly, was labeled as having osteopenia; in fact, the term osteopenia does not refer to a disease but rather to an old radiologic term that has turned into a syndrome to describe an individual with moderately low BMD compared with peak bone mass. However, at this age and with her current menopausal status, her peak bone mass (rather than the degree of bone loss after her menopause) is the primary determinant of her current BMD. Her T-score is still within 2 SD of the average for a 35-year-old woman (and is only about 1 SD below average for her age).(2) As such, this “score” represents a person who has a BMD within the normal range for this measurement technique. Therefore, she may or may not require any therapeutic intervention at this stage, depending again on her risk assessment, the established efficacy of potential treatments, her willingness to comply, and the establishment of a final outcome measure (i.e., new fracture, change in BMD, change in marker, or another arbitrary endpoint). LR had no family history of osteoporosis and never sustained a fracture; therefore, her absolute risk for an osteoporotic spine, wrist, or hip fracture over the next 5 years would be very low and in the range of <0.12%/year(3) (Fig. 1). Determining other factors such as personal and family history of fractures, height loss since young adulthood, and current weight might help in determining her overall risk status. The use of a bone marker to assess the current rate of bone resorption might provide additional insight, although in this age group, its ability to predict fractures has never been established. Similarly, no treatments have been proven to reduce fracture risk among women in their 50s with osteopenia, although several treatments have been shown to reduce bone loss. Short- and long-term efficacy of treatments on fracture risk are unknown for women in this age group. Major interventions such as a bisphosphonate or parathyroid hormone (PTH), although probably effective in reducing her risk of spine and non-spine (primarily wrist) fractures, might be considered unjustified based on her absolute risk at the age of 52, and a number needed to treat (NNT) of approximately 2000 (i.e., the number of women you would have to treat to prevent one spine or non-spine fracture).(3,4) On the other hand, employment of simple preventive approaches could forestall future bone loss and delay or prevent the onset of osteoporosis in her seventh, eighth, or ninth decade of life. Before publication of several Women's Health Initiative (WHI) studies, most practitioners would have recommended hormone replacement therapy (HRT), which could attenuate bone loss and effectively treat hot flashes.(5,6) But LR, even at her age, is more likely to have an adverse event from HRT over the next 5 years (i.e., venous thrombosis, myocardial infarction, stroke, or breast cancer) than a beneficial outcome (fracture risk reduction, improved quality of life), particularly considering her low absolute risk.(5,7) Hence, other approaches should be considered. For example, low-dose estrogen (i.e., 0.30 mg of conjugated equine estrogen) has proven skeletal efficacy with respect to preventing bone loss and may reduce hot flashes. However, overall atherosclerotic or cancer risk with this type of therapy is unknown, and in LR, who has a uterus, it would have to be combined with a progestational agent.(8) Furthermore, short-term estrogen replacement therapy (<5 years) is unlikely to affect long-term fracture risk.(9) Raloxifene is an option because it can prevent bone loss; however, it would be less efficacious as a treatment aimed at preventing fractures because, once again, the NNT is quite high.(3,4) Also, whereas raloxifene may ultimately lower the risk of breast cancer, it may aggravate hot flashes in this age group.(10)

Table 1

Table Table 1. Summary of a Case-Based Approach to Osteoporosis Management
original image
Figure FIG. 1..

Identification of high-risk patients: 5-year fracture risk. The highest-risk patients are those over 70 years of age; patients 4 and 5 are within this very high-risk category. Patient 3 may be at very high risk based on his history of Crohn's disease and glucocorticoid use, but his absolute risk of a nonvertebral fracture is not quantifiable.(56) Figure adapted from Cooper et al.(57)

It should be noted that some women who consume calcium supplements (i.e., 1000 mg/day) and vitamin D (400–800 IU/day) can slow their endogenous rates of resorption and prevent bone loss, especially when complemented by an adequate exercise program.(3,11) Regardless of the therapeutic options, most clinicians would recommend (and we agree, although the evidence is not very strong) for general bone health, a follow-up BMD in 2–3 years, at which time decisions by both the practitioner and patient could be made regarding future therapy.

This woman declined any pharmacologic interventions and instead agreed to a regimen of calcium supplementation (500 mg, two times per day), a multivitamin, and an exercise program. She also began to experiment with several soy preparations, although there is no evidence that these agents reduce fracture risk or prevent bone loss.

CASE 2: A POSTMENOPAUSAL WOMAN WHO RECENTLY DISCONTINUED HRT BUT HAS LOW BMD

RG is a 68-year-old woman who has been on HRT since menopause. She initially took HRT for hot flashes and continued it because she was told of the benefits for her heart and bones. When she learned that the results of the WHI showed significant increases in cardiovascular disease, deep vein thrombosis, and breast cancer after 5 years of HRT,(12,13) she elected to discontinue the HRT. She scheduled an office visit with her physician to determine if she needed additional therapy to prevent osteoporosis. She has not taken calcium or vitamin D supplements but does take a daily multivitamin. She is lactose intolerant. She has lost 2 in in height. Approximately 10 years ago, she sustained a forearm fracture when she slipped on ice. She knows of no family history of osteoporosis.

When RG turned 65, she had a BMD test, which revealed a spine T-score of −2.0, consistent with osteopenia, and a hip T-score of −2.2, also consistent with osteopenia according to World Health Organization (WHO) criteria.(2,14,15) Her relatively low BMD and history of a forearm fracture are consistent with a clinical diagnosis of osteoporosis. In addition, her lack of calcium intake could further contribute to bone loss. Based on her BMD and other above-mentioned risk factors, her absolute risk of fracture in 5 years will be relatively high, assuming the cumulative effects on bone of 15 years of HRT diminishes with time.

Because RG has already sustained a clinical fracture, it would be important to exclude secondary causes of bone loss. This can be done in a relatively focused manner by obtaining a serum calcium to exclude hyperparathyroidism, thyroid-stimulating hormone (TSH) to exclude hyperthyroidism, 25-hydroxyvitamin D to exclude vitamin D deficiency, and 24-h urinary calcium to assess malabsorption of calcium and renal abnormalities.(16) RG's values, however, were all within the normal range. Hence, she should begin calcium supplementation at 1200 mg/day in divided doses and vitamin D supplementation at 800 IU/day, as suggested by the National Osteoporosis Foundation and in agreement with the National Institutes of Health Consensus Conference.(17,18) Her multivitamin contains 400 IU of vitamin D, so an additional 400 IU are needed. She should also be encouraged to perform weight-bearing exercises, such as walking or strength training, for a minimum of 30 minutes, three times per week.

Her decision to discontinue HRT places her at risk for an increased rate of bone loss. Previous studies have shown that discontinuation of HRT in this age group can be associated with significant bone loss of up to 4% in the first year and continued accelerated bone loss.(19) Therefore, she should begin an additional therapy to prevent bone loss and fractures, especially with her history of a clinical fracture. Appropriate alternatives include once-weekly bisphosphonate therapy (both alendronate and risedronate have been shown to reduce vertebral and nonvertebral, including hip, fractures by 30–50%)(20–22) or the selective estrogen receptor modulator raloxifene (shown to reduce vertebral fractures by approximately 50%).(23) It is advisable that a follow-up BMD test be performed no sooner than 2 years after therapy is initiated.

This woman agreed to therapy with alendronate 70 mg once per week. Calcium supplementation was started (500 mg, two times per day) in addition to a pure vitamin D supplement of 400 IU/day, and her multivitamin was continued.

CASE 3: GLUCOCORTICOID-INDUCED OSTEOPOROSIS IN A MALE

WG is a 60-year-old man on long-term glucocorticoids (10 mg/day or more for >20 years) with a diagnosis of Crohn's disease. He has suffered multiple vertebral fractures for a total of 3 in of height loss. He has had three intestinal surgeries, exhibits easy bruising, and has a Cushingoid appearance. His BMD T-score is −1.6 at the lumbar spine and −1.0 at the femoral neck. Calcium intake is 600 mg/day, at best, because of gastrointestinal (GI) intolerance.

Exogenous use of glucocorticoids is the most common secondary cause of osteoporosis.(24) More than one-half of all individuals treated chronically with steroids will develop osteoporosis.(24) The development of glucocorticoid-induced osteoporosis (GIO) is a function of the chronic inflammatory disease for which steroids are prescribed and the direct negative effects of glucocorticoids on bone formation. Rapid bone loss from glucocorticoid therapy is often noted in the first 6 months of treatment and is more often associated with a reduction in markers of bone formation than an enhancement in markers of bone resorption.(25) Frequently, BMD can be misleadingly normal or only modestly decreased, as in the case of WG, yet the individual continues to sustain multiple fractures at various skeletal sites. Anecdotally, patients with the Cushingoid phenotype as a result of exogenous glucocorticoids invariably have severe osteoporosis; moreover, there is probably a subset of individuals on long-term steroids who do not lose bone mass, never sustain fractures, and have normal BMDs. Identifying those at highest risk for GIO is an important goal, although it is more complicated than simply calculating the dose and duration of steroid use.

For WG, his underlying risk for new fractures is high for several reasons including his previous fracture history, his modestly low BMD, his age, his Cushingoid appearance, and his disease state. Crohn's disease contributes to a greater risk of osteoporosis, in part because of the inflammatory nature of the disorder, the frequent association of Crohn's disease (especially in those with multiple surgeries) with vitamin D deficiency, physical inactivity because of disease severity, the effects of other anti-inflammatory drugs on bone remodeling, and the possibility of primary or secondary hypogonadism.(26,27)

There is little doubt that WG requires aggressive therapy for his osteoporosis. Therapy begins by providing adequate calcium intake and identifying any vitamin D deficiency or insufficiency. Vitamin D deficiency can usually be corrected by using 50,000 U of vitamin D2 (i.e., ergocalciferol) or D3 (i.e., cholecalciferol) given orally once weekly for 3 months. Other hydroxylated vitamin D preparations could also be considered. Serum 25-hydroxyvitamin D level should be measured 3 months after initiation of the vitamin D preparation. Antiresorptive therapy may be initiated either simultaneously with vitamin D or after correction of any vitamin D deficiency. Three bisphosphonates (i.e., alendronate, risedronate, or etidronate; etidronate is not approved in the United States) could be considered, all of which have been shown in randomized, placebo-controlled trials to prevent fractures in GIO.(25,28–32) If the patient had a low serum testosterone concentration, a reasonable case could be made for androgen replacement, either parenterally or transcutaneously. However, careful follow-up is required with testosterone replacement, including regular examinations of the prostate and prostate-specific antigen (PSA) measurements. In men not on glucocorticoids, gonadal status did not influence the skeletal response to bisphosphonate therapy.(33)

Unfortunately, there are no other U.S. Food and Drug Administration (FDA)-approved therapies for this condition. PTH(1–34) might be considered in this case, although it is not recognized by regulatory agencies as an established treatment for GIO.(34,35) One randomized, placebo-controlled trial by Lane et al.(35) with a very small number of subjects found that PTH could significantly enhance trabecular BMD in the spine in women receiving glucocorticoids and concurrent estrogen replacement therapy. However, that is the only published study. Fracture efficacy in GIO with PTH has never been firmly established, and there is likely to be significant clinical heterogeneity with respect to skeletal responsiveness to intermittent PTH treatment among osteoporotic individuals of any etiology. Hence, despite growing marketplace use of PTH for GIO, some caution must be exercised to define the appropriate individual before embarking on therapy. Follow-up BMD measurements have never been shown to influence the course of steroid-induced osteoporosis, nor for that matter, postmenopausal osteoporosis, but still might play a role in identifying individuals who may remain at high risk with persistent bone loss and/or fractures. The key to successful management of GIO is not repeated BMD measurements, but very close surveillance with particular attention to underlying disease severity, prevention at the start of glucocorticoid treatment, living conditions, fall frequency, comorbid states, and socioeconomic conditions.

This man was started on oral ergocalciferol 50,000 U once per week. After 1 month, the patient was given once weekly bisphosphonate, but he developed GI intolerance. He elected to use etidronate 400 mg once daily for 2 weeks every 3 months.

CASE 4: SEVERE POSTMENOPAUSAL OSTEOPOROSIS

RW is a 70-year-old woman with a history of low BMD and multiple vertebral fractures who has been on once weekly bisphosphonate, calcium, and vitamin D for 2 years. Her T-score in the spine initially was −3.0. She presents 2 years after initiation of therapy with a T-score in the spine of −3.5, in the femoral neck of −3.0, and new osteoporotic fractures of the radius and thoracic spine. She has significant interscapular pain. Her primary physician has recommended vertebroplasty for her newly fractured T7 vertebrae.

RW has full-blown postmenopausal osteoporosis with ongoing osteoporotic fractures despite antiresorptive therapy. She has sustained both vertebral and radial fractures with minimal or no trauma. Her 5-year absolute risk of a nonvertebral fracture without treatment 2 years ago was very high (i.e., close to 9%).(3,4) She was appropriately placed on a bisphosphonate along with calcium and vitamin D, which should have lowered her absolute risk. However, in the ensuing 2 years, she actually lost BMD and sustained two new fractures within a relatively short span of time. Her spine fracture is painful, and an invasive procedure was recommended to reduce pain.

The management of RW is not straightforward. First, let us consider changes in her BMD. Although loss of BMD after 2 years of bisphosphonate treatment is not rare, the magnitude of loss in RW (i.e., 0.5 SD decline in spine BMD) is remarkable and troublesome.(36) Immediately, we must consider the following, assuming no measurement error in spine BMD either initially or at year 2:

1. Is she taking her bisphosphonate? Although the response to this question should be an easy yes or no, often the answer is not straightforward (also see 2 below). Moreover, the degree of compliance is clearly in the eyes of the beholder. In clinical trials of osteoporosis medications, compliance depends on many factors including the investigative site, the type of drug being used, and the adverse event profile. It is even more heterogeneous in clinical practice. And, although once-weekly bisphosphonate therapy has been a boon to patients and has captured the marketplace, figures on compliance, especially among the elderly, are more difficult to ascertain. A very high bone turnover marker would suggest noncompliance or incomplete absorption of the bisphosphonate, but a normal marker level (i.e., within the premenopausal range) would not be particularly useful to the clinician.

2. Is the bisphosphonate being absorbed? Few women in randomized trials of alendronate or risedronate lose more than 5% of their spine BMD after 2 years of bisphosphonate treatment.(37) It is certainly conceivable that she cannot absorb the drug, that she is taking it inappropriately, or that she is a “true” nonresponder. As noted above, a biochemical marker of bone resorption that did not suppress with treatment or was significantly elevated might prove useful. However, because of intrinsic laboratory variance and subject heterogeneity, markers often do not provide a clear-cut answer. Indeed, the definition of a clinical “nonresponder” to bisphosphonates is obtuse and could reflect continued bone loss, new fractures, a combination of both, or refractory bone pain.

3. Are there secondary causes of osteoporosis that are contributing to her bone loss and fractures? This is a possibility that should be considered, and as noted above (case 3), vitamin D deficiency syndromes can result in osteomalacia and worsening skeletal fragility. Celiac sprue may coexist with postmenopausal osteoporosis or contribute to its severity. Celiac sprue is almost always associated with very low levels of serum 25-hydroxyvitamin D and high levels of PTH. Tumors, especially hematologic, could be a factor, although this is more unusual. Other systemic diseases or conditions such as primary hyperparathyroidism, occult use of glucocorticoids (or endogenous Cushing's disease), prolonged immobility, and subclinical thyrotoxicosis should be considered.

4. What therapeutic intervention should be considered assuming there are no secondary causes of her bone loss? If no secondary causes are found, it must be concluded that this patient has accelerated osteoporosis, is at very high risk for future fractures, and will require further aggressive intervention. Vertebroplasty to reduce pain and improve mobility could be considered; however, there are risks associated with this procedure, some known, but many still unknown. For example, there may be a greater risk of new vertebral fractures in the bones adjacent to the newly fractured thoracic vertebrae, T7.(38–42) Epidural leakage of cement, complications from the anesthesia required for kyphoplasty, and reflex sympathetic dystrophy also may complicate her course postintervention. Because there are no randomized, placebo-controlled trials of vertebroplasty or kyphoplasty, it is difficult to judge whether this procedure will be successful, although some patients get remarkable and complete pain relief.

With respect to pharmacologic interventions, switching her to another once-weekly bisphosphonate or to intravenous therapy with pamidronate or zoledronic acid might be considered. However, the latter two drugs have not been approved by the FDA for the treatment of postmenopausal osteoporosis, and their fracture efficacy has not been established in randomized, placebo-controlled trials. Switching to calcitonin or raloxifene is palatable to the practitioner, but it is unlikely that these weaker agents would prevent further nonvertebral fractures.(32) PTH(1–34) 20 μg (teriparatide) for 18 months administered daily might be a reasonable choice, especially because she has very low BMD and multiple fractures.(34,43–47) It is also likely the patient would take PTH, knowing full well that her absolute risk of a subsequent nonvertebral fractures probably approaches 10% per year (see Fig. 1).(4) However, it is not at all clear that PTH in addition to ongoing bisphosphonate therapy is more advantageous than monotherapy. Indeed, there may be an impaired skeletal response to PTH in the setting of previous or concurrent bisphosphonate treatment.(48,49) Moreover, the cost and its efficacy in relation to the bisphosphonates must also be factored into the equation. Other combinations of antiresorptives are not likely to be any more effective than a single antiresorptive therapy alone, particularly in respect to antifracture efficacy.

This patient is at very high risk for subsequent fractures, and the reader must be reminded that the best we usually can do in such women is a 50% reduction in their relative risk of a new nonvertebral or vertebral fracture. As such, she may belong to a very small group of individuals whose bone quality is highly compromised, and aggressive therapy may, at best, only serve to prevent more progressive disease. Notwithstanding these considerations, RW needs comprehensive management for pain relief and a therapeutic plan for the prevention of future fractures. Switching to another bisphosphonate or PTH monotherapy seems most appropriate. These individuals are the most challenging for clinicians who specialize in metabolic bone diseases and also offer the best proof that we have yet to cure this disease.

This woman was treated aggressively for pain relief with narcotics. She refused vertebroplasty and was switched to another oral bisphosphonate given once weekly. Her N-telepeptide (NTx) value was 55 bone collagen equivalence (BCE)/mmol creatinine. Her 25(OH)D level was 35 ng/ml, so her multivitamin was continued; her calcium supplementation was increased to 1500 mg/day.

CASE 5. AGE-RELATED OSTEOPOROSIS

PR is an 80-year-old frail, community-dwelling woman living alone. Although she has no history of fractures, she does report intermittent falls during the year. She takes 1000 mg of calcium each day in the morning and a daily multivitamin. She does not go out in the sun for fear of skin cancer and wrinkles. Because of her history of falling and her uncertain gait, she walks very little. Her BMD revealed a T-score of −2.8 at the hip, consistent with osteoporosis, and a T score of −2.0 at the spine, consistent with osteopenia. She has a long history of heartburn and gastroesophageal reflux disease (GERD), which is currently treated with a proton pump inhibitor. She also has hypertension, which is treated with a beta blocker.

Age-related osteoporosis is often overlooked as a primary diagnosis in PR's age group. However, she is at very high risk of osteoporotic fractures that could significantly alter her overall quality of life. Hence, older, frail patients should be evaluated for both low BMD and falls. Although fall prevention programs have not been shown to reduce fracture risk in a randomized trial, they have been shown to reduce falls by 31%.(50) A falls assessment should include an examination of the patient's medications that can cause hypotension and/or dizziness (e.g., beta blockers), and the patient's house should be evaluated for a safe environment. A fall prevention home assessment involves ensuring that there are no loose rugs or cords, well-lit stairways with handrails, skid-free floors in the bathroom along with grab bars, and good bedside lighting. Finally, these patients should be evaluated for strength training exercises to improve their balance and overall strength.

In addition to the falls assessment, this patient would also require a focused work-up to examine the most common secondary causes of bone loss. Vitamin D deficiency is common in this age group.(51) This patient had a serum 25-hydroxyvitamin D level of less than 8 ng/ml (normal range, 10–68 ng/ml), which is considered true vitamin D deficiency. Therefore, she should be treated with 50,000 U of vitamin D once per week for 3 months. In older women who are not vitamin D deficient, 800 IU of vitamin D per day is recommended. Alternatively, a recent randomized clinical trial showed that 100,000 U of oral vitamin D given every 4 months significantly reduced nonvertebral fractures.(52) Although she takes 1000 mg of calcium per day, she should be instructed to take this in divided doses of 500 mg twice per day (at breakfast and dinner) to improve absorption. Finally, she should be enrolled in some physical therapy/exercise program to improve her overall strength, walking, gait, and balance.

Once other secondary causes of bone loss are eliminated, she should also be started on an anti-osteoporosis medication. With her history of osteoporosis by densitometry and her history of falling, her absolute risk of a nonvertebral fracture is very high (approaching 10%/year; see Fig. 1). Her therapeutic options should focus on agents that have been shown to reduce hip fractures. This would include the once weekly bisphosphonates: alendronate and risedronate. Even patients with GERD, who are asymptomatic and well-controlled with an H2 blocker or proton pump inhibitor, can be treated with a once-weekly bisphosphonate. If symptoms of epigastric distress persist with these agents and the proton pump inhibitor, it is reasonable to change treatments. The next best line of therapy would be subcutaneous daily PTH or teriparatide. This has been shown to decrease vertebral and nonvertebral fractures by approximately 65% and 53%, respectively.(47) Because PTH could cause some nausea and dizziness, this should be given with caution in elderly, frail patients who live alone. Although HRT has been shown to decrease hip fractures, it would not be a good option for this patient because of the potential increased risk of cardiovascular disease, breast cancer, and thromboembolic phenomena (e.g., stroke), as well as the issue of uterine bleeding.(12) Raloxifene has been shown to reduce vertebral fractures by approximately 50%, but it has not been shown to reduce nonvertebral and hip fractures.(23) Therefore, for PR, who has osteoporosis at the hip and who would have to discontinue the therapy for short periods of immobility, this would not be a viable alternative. In the future, a once-yearly intravenous bisphosphonate might provide a reasonable option, assuming that these more potent bisphosphonates have been shown to be safe with respect to mineralization and can reduce risk of fracture.

Finally, in addition to the medical therapy, another alternative for PR would be to consider hip protectors. Data on the efficacy of hip protectors in the prevention of hip fractures is equivocal, but one randomized trial reported a 40% reduction in hip fractures.(53–55) Poor compliance is one of the major reasons why many of these studies do not provide hip fracture reduction. Therefore, PR would benefit from the medical therapy and hip protector, if worn. It would be important to recheck her BMD in 2 years to assess her therapeutic response.

This patient was given 50,000 U of ergocalciferol weekly for 3 months. Vitamin D was checked, and the patient was started on risedronate 35 mg once per week. She also was placed in a physical therapy program for muscle conditioning. She refused a hip protector.

DISCUSSION

In conclusion, all women beyond menopause need to be assessed for multiple risk factors related to osteoporosis. In addition, all patients on glucocorticoids and men with unexplained back pain and height loss should be evaluated for their subsequent osteoporotic risk. Based on clinical and bone density risk factors, health care providers can arrive at risk predictions for any given individual. All patients should be counseled on appropriate intake of calcium (1200 mg/day in divided doses), vitamin D (400–800 IU/day), and weight-bearing exercise, regardless of whether other therapeutic regimens are being considered. Pharmacologic alternatives should be based on the sum of the patient's clinical risk factors and bone density determination. Then, in conjunction with other medications and consideration of concurrent medical problems, an appropriate therapeutic course based on the evidence can be determined. Although osteoporosis is common, morbid, and costly, early detection using risk factor stratification and BMD testing should allow optimal therapeutic intervention, based on reliable evidence, including calcium, vitamin D supplementation, and in some instances, antiresorptives or anabolic therapy.

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