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Context: Risedronate, a potent bisphosphonate, has been shown to be effective in the treatment of Paget disease of bone and other metabolic bone diseases but, to our knowledge, it has not been evaluated in the treatment of established postmenopausal osteoporosis.Objective: To test the efficacy and safety of daily treatment with risedronate to reduce the risk of vertebral and other fractures in postmenopausal women with established osteoporosis.Design, Setting, and Participants: Randomized, double-blind, placebo-controlled trial of 2458 ambulatory postmenopausal women younger than 85 years with at least 1 vertebral fracture at baseline who were enrolled at 1 of 110 centers in North America conducted between December 1993 and January 1998.Interventions: Subjects were randomly assigned to receive oral treatment for 3 years with risedronate (2.5 or 5 mg/d) or placebo. All subjects received calcium, 1000 mg/d. Vitamin D (cholecalciferol, up to 500 IU/d) was provided if baseline levels of 25-hydroxyvitamin D were low.Main Outcome Measures: Incidence of new vertebral fractures as detected by quantitative and semiquantitative assessments of radiographs; incidence of radiographically confirmed nonvertebral fractures and change from baseline in bone mineral density as determined by dual x-ray absorptiometry.Results: The 2.5 mg/d of risedronate arm was discontinued after 1 year; in the placebo and 5 mg/d of risedronate arms, 450 and 489 subjects, respectively, completed all 3 years of the trial. Treatment with 5 mg/d of risedronate, compared with placebo, decreased the cumulative incidence of new vertebral fractures by 41 % (95% confidence interval [CI], 18%-58%) over 3 years (11.3 % vs 16.3%; P= .003). A fracture reduction of 65% (95% CI, 38%-81 %) was observed after the first year (2.4% vs 6.4%; P<.001). The cumulative incidence of nonvertebral fractures over 3 years was reduced by 39% (95% CI, 6%-61 %) (5.2 % vs 8.4%; P = .02). Bone mineral density increased significantly compared with placebo at the lumbar spine (5.4% vs 1.1 %), femoral neck (1.6% vs -1.2%), femoral trochanter (3.3% vs -0.7%), and midshaft of the radius (0.2% vs -1.4%). Bone formed during risedronate treatment was histologically normal. The overall safety profile of risedronate, including gastrointestinal safety, was similar to that of placebo.Conclusions: These data suggest that risedronate therapy is effective and well tolerated in the treatment of women with established postmenopausal osteoporosis. [ABSTRACT FROM AUTHOR]

Background: Endometriosis is a chronic, estrogen-dependent condition that causes dysmenorrhea and pelvic pain. Elagolix, an oral, nonpeptide, gonadotropin-releasing hormone (GnRH) antagonist, produced partial to nearly full estrogen suppression in previous studies.Methods: We performed two similar, double-blind, randomized, 6-month phase 3 trials (Elaris Endometriosis I and II [EM-I and EM-II]) to evaluate the effects of two doses of elagolix - 150 mg once daily (lower-dose group) and 200 mg twice daily (higher-dose group) - as compared with placebo in women with surgically diagnosed endometriosis and moderate or severe endometriosis-associated pain. The two primary efficacy end points were the proportion of women who had a clinical response with respect to dysmenorrhea and the proportion who had a clinical response with respect to nonmenstrual pelvic pain at 3 months. Each of these end points was measured as a clinically meaningful reduction in the pain score and a decreased or stable use of rescue analgesic agents, as recorded in a daily electronic diary.Results: A total of 872 women underwent randomization in Elaris EM-I and 817 in Elaris EM-II; of these women, 653 (74.9%) and 632 (77.4%), respectively, completed the intervention. At 3 months, a significantly greater proportion of women who received each elagolix dose met the clinical response criteria for the two primary end points than did those who received placebo. In Elaris EM-I, the percentage of women who had a clinical response with respect to dysmenorrhea was 46.4% in the lower-dose elagolix group and 75.8% in the higher-dose elagolix group, as compared with 19.6% in the placebo group; in Elaris EM-II, the corresponding percentages were 43.4% and 72.4%, as compared with 22.7% (P<0.001 for all comparisons). In Elaris EM-I, the percentage of women who had a clinical response with respect to nonmenstrual pelvic pain was 50.4% in the lower-dose elagolix group and 54.5% in the higher-dose elagolix group, as compared with 36.5% in the placebo group (P<0.001 for all comparisons); in Elaris EM-II, the corresponding percentages were 49.8% and 57.8%, as compared with 36.5% (P=0.003 and P<0.001, respectively). The responses with respect to dysmenorrhea and nonmenstrual pelvic pain were sustained at 6 months. Women who received elagolix had higher rates of hot flushes (mostly mild or moderate), higher levels of serum lipids, and greater decreases from baseline in bone mineral density than did those who received placebo; there were no adverse endometrial findings.Conclusions: Both higher and lower doses of elagolix were effective in improving dysmenorrhea and nonmenstrual pelvic pain during a 6-month period in women with endometriosis-associated pain. The two doses of elagolix were associated with hypoestrogenic adverse effects. (Funded by AbbVie; Elaris EM-I and EM-II ClinicalTrials.gov numbers, NCT01620528 and NCT01931670 .). [ABSTRACT FROM AUTHOR]

Purpose: To determine the efficacy and safety of cyclical etidronate for up to 7 years in the treatment of postmenopausal osteoporosis and to examine the effects of discontinuing treatment after 2 or 5 years of therapy.Patients and Methods: Patients were randomized at entry into the original study in 1986 to blinded treatment for 2 years with either a calcium (placebo) or an intermittent cyclical etidronate regimen, which most patients continued for a third year. Following this phase of the study, patients were enrolled into an open-label, follow-up study (years 4 and 5), during which all patients received cyclical etidronate treatment. In the present double-blind study (years 6 and 7), patients were rerandomized to receive intermittent cyclical therapy with either etidronate or placebo; all patients received calcium. The treatment regimen consisted of 400 mg/day etidronate or placebo for 14 days, followed by 76 days of elemental calcium (500 mg/day); this cycle was repeated approximately 4 times in each year. Of the 193 patients who continued in years 6 and 7 of the study, 93 were randomized to receive cyclical etidronate and 100 were randomized to receive calcium only. For purposes of efficacy analyses, patients were categorized by their total years of cumulative etidronate treatment (7, 5, 4, or 2 years). There were 51, 46, 42, and 54 patients in the 7-, 5-, 4-, and 2-year groups, respectively. Annual assessments included lumbar spine bone mineral density (BMD), as measured by densitometry, and vertebral radiographs.Results: The groups receiving cyclical etidronate during this 2-year study period (7- and 4-year groups) had statistically significant mean percent increases in spinal BMD of 1.8% and 2.2%, respectively (P < 0.05) at the week 104 observation time. The 5- and 2-year groups, which did not receive etidronate during this period, had mean values of 1.4% and 0.2%, respectively (not significant) at week 104. In the 7-, 5-, 4-, and 2-year groups, the increases in spinal BMD at the end of 7 years were 7.6%, 8.6%, 8.1%, and 3.9%, respectively; these values were statistically significant for all groups compared with original baseline (year 0) (P < 0.05). BMD of the femur and wrist was maintained throughout the 7-year period. The incidence and rate of vertebral fractures were lowest in patients with the longest exposure to etidronate. Etidronate was well tolerated during the study, with low incidences of gastrointestinal side effects and nonvertebral fractures.Conclusions: Long-term cyclical etidronate is a safe, effective, and well-tolerated treatment for postmenopausal osteoporosis. Bone mass is maintained for at least 2 years after treatment with etidronate is stopped; however, further gains in spinal bone mass are seen in patients who continue therapy. [ABSTRACT FROM AUTHOR]

Abaloparatide increased ultradistal radius bone mineral density (BMD) in the Abaloparatide Comparator Trial in Vertebral Endpoints (ACTIVE) trial. Over the subsequent 24 months in ACTIVExtend, ultradistal radius BMD gains were maintained with alendronate. Conversely, 1/3 radius BMD remained stable during ALN treatment in ACTIVExtend after decreasing during ACTIVE., Introduction: Abaloparatide (ABL) increased femoral neck, total hip, and lumbar spine bone mineral density (BMD) in postmenopausal women with osteoporosis and decreased the risk of vertebral and nonvertebral fractures in ACTIVE. Effects on fracture risk and BMD were maintained subsequently with alendronate (ALN) in ACTIVExtend. In a prespecified subanalysis of ACTIVE, ABL also increased BMD at the ultradistal radius. Our objective was to determine the efficacy of ABL followed by ALN vs placebo (PBO) followed by ALN on forearm BMD and fracture risk over 43 months in ACTIVExtend., Methods: Ultradistal and 1/3 radius BMD (ACTIVE baseline to month 43) were measured (ABL/ALN, n = 213; PBO/ALN, n = 233). Wrist fracture rates were estimated for the ACTIVExtend intent-to-treat population (ABL/ALN, n = 558; PBO/ALN, n = 581) by Kaplan-Meier (KM) method., Results: At cumulative month 25, mean increase from ACTIVE baseline in ultradistal radius BMD was 1.1% (standard error, 0.49%) with ABL/ALN vs - 0.8% (0.43%) with PBO/ALN (P < 0.01). BMD increases with ABL were maintained with ALN through month 43 in ACTIVExtend. BMD decreases at the 1/3 radius in ACTIVE (similar with ABL and PBO) were maintained through 24 months of ALN treatment in ACTIVExtend. Wrist fractures over 43 months occurred in 15 women with ABL/ALN (KM estimate, 2.8%) and 20 with PBO/ALN (KM estimate, 3.6%) (HR = 0.77, 95% CI 0.39, 1.50; P = not significant)., Conclusion: Ultradistal radius BMD gains following treatment with ABL in ACTIVE were maintained over 24 months of ALN treatment in ACTIVExtend. Conversely, 1/3 radius BMD remained stable during ALN treatment in ACTIVExtend after decreasing during ACTIVE., Trial Registration: ClinicalTrials.gov : NCT01657162 submitted July 31, 2012.

We investigated the factors associated with readiness for initiating osteoporosis treatment in women at high risk of fracture. We found that women in the contemplative stage were more likely to report previously being told having osteoporosis or osteopenia, acknowledge concern about osteoporosis, and disclose prior osteoporosis treatment., Introduction: Understanding factors associated with reaching the contemplative stage of readiness to initiate osteoporosis treatment may inform the design of behavioral interventions to improve osteoporosis treatment uptake in women at high risk for fracture., Methods: We measured readiness to initiate osteoporosis treatment using a modified form of the Weinstein Precaution Adoption Process Model (PAPM) among 2684 women at high risk of fracture from the Activating Patients at Risk for OsteoPOroSis (APROPOS) clinical trial. Pre-contemplative participants were those who self-classified in the unaware and unengaged stages of PAPM (stages 1 and 2). Contemplative participants were those in the undecided, decided not to act, or decided to act stages of PAPM (stages 3, 4, and 5). Using multivariable logistic regression, we evaluated participant characteristics associated with levels of readiness to initiate osteoporosis treatment., Results: Overall, 24% (N = 412) self-classified in the contemplative stage of readiness to initiate osteoporosis treatment. After adjusting for age, race, education, health literacy, and major osteoporotic fracture in the past 12 months, contemplative women were more likely to report previously being told they had osteoporosis or osteopenia (adjusted odds ratio [aOR] (95% CI) 11.8 (7.8-17.9) and 3.8 (2.5-5.6), respectively), acknowledge concern about osteoporosis (aOR 3.5 (2.5-4.9)), and disclose prior osteoporosis treatment (aOR 4.5 (3.3-6.3)) than women who self-classified as pre-contemplative., Conclusions: For women at high risk for future fractures, ensuring women's recognition of their diagnosis of osteoporosis/osteopenia and addressing their concerns about osteoporosis are critical components to consider when attempting to influence stage of behavior transitions in osteoporosis treatment.

Purpose: Wrist fractures are common, contribute significantly to morbidity in women with postmenopausal osteoporosis, and occur predominantly at the ultradistal radius, a site rich in trabecular bone. This exploratory analysis of the phase 3 ACTIVE study evaluated effects of abaloparatide versus placebo and teriparatide on forearm bone mineral density (BMD) and risk of wrist fracture., Methods: Forearm BMD was measured by dual energy X-ray absorptiometry in a subset of 982 women from ACTIVE, evenly distributed across the three treatment groups. Wrist fractures were ascertained in the total cohort (N = 2463)., Results: After 18 months, ultradistal radius BMD changes from baseline were 2.25 percentage points greater for abaloparatide compared with placebo (95% confidence interval (CI) 1.38, 3.12, p < 0.001) and 1.54 percentage points greater for abaloparatide compared with teriparatide (95% CI 0.64, 2.45, p < 0.001). At 18 months, 1/3 radius BMD losses (versus baseline) were similar for abaloparatide compared with placebo (-0.42; 95% CI -1.03, 0.20; p = 0.19) but losses with teriparatide exceeded those of placebo (-1.66%; 95% CI -2.27, -1.06; p < 0.001). The decline with abaloparatide was less than that seen with teriparatide (group difference 1.22%; 95% CI 0.57, 1.87; p < 0.001). The radius BMD findings, at both ultradistal and 1/3 sites, are consistent with the numerically lower incidence of wrist fractures observed in women treated with abaloparatide compared with teriparatide (HR = 0.43; 95% CI 0.18, 1.03; p = 0.052) and placebo (HR = 0.49, 95% CI 0.20, 1.19, p = 0.11)., Conclusions: Compared with teriparatide, abaloparatide increased BMD at the ultradistal radius (primarily trabecular bone) and decreased BMD to a lesser extent at the 1/3 radius (primarily cortical bone), likely contributing to the numerically lower wrist fracture incidence observed with abaloparatide.

The aim of this study was to provide confirmation that once-weekly dosing with 70 mg of alendronate (seven times the daily oral dose) and twice-weekly dosing with 35 mg is equivalent to the 10-mg once-daily regimen and to gain more extensive safety experience with this new dosing regimen. Twelve hundred fifty-eight postmenopausal women (aged 42-95 years) with osteoporosis (bone mineral density [BMD] of either lumbar spine or femoral neck at least 2.5 SDs below peak young adult mean or prior vertebral or hip fracture) were assigned to receive oral once-weekly alendronate, 70 mg (n = 519); twice-weekly alendronate, 35 mg (n = 369); or daily alendronate 10 mg (n = 370) for a total of 2 years of double-blind experience. Mean BMD increases from baseline (95% CI) at 24 months in the once-weekly, twice-weekly, and daily treatment groups, respectively, were 6.8% (6.4, 7.3), 7.0% (6.6,7.5), and 7.4% (6.9,7.8) at the lumbar spine and 4.1% (3.8,4.5), 4.3% (3.9,4.7), and 4.3% (3.9,4.7) at the total hip. These increases in BMD as well as the BMD increases at the femoral neck, trochanter, and total body and the reductions of biochemical markers of bone resorption (urinary cross-linked N-telopeptides of type I collagen [NTx]) and bone formation (serum bone-specific alkaline phosphatase [BSAP]) were similar for the three dosing regimens. All treatment regimens were well tolerated with a similar incidence of upper gastrointestinal (GI) adverse experiences. The incidence rates of clinical fractures, captured as adverse experiences, were similar among the groups. The 2-year results confirm the conclusion reached after 1 year that once-weekly alendronate is therapeutically equivalent to daily dosing, providing patients with a more convenient dosing option that may potentially enhance adherence to therapy.

Background: The occurrence of kidney stones is disproportionate in the southern region of the United States. Risk factors for the occurrence of kidney stones in this geographic area have not been reported previously., Methods: The Women's Health Initiative (WHI) is an ongoing multicenter clinical investigation of strategies for the prevention of common causes of morbidity and mortality among postmenopausal women. A case-control ancillary study was conducted on 27,410 (white or black) women enrolled in the 9 southern WHI clinical centers. There were 1,179 cases (4.3%) of kidney stones at the baseline evaluation. Risk factors for stone formation were assessed in cases versus age- and race-matched control subjects., Results: Risk factors (univariate) included low dietary potassium (2,404 versus 2,500 mg/day, P = 0.006), magnesium (243 versus 253 mg/day, P = 0.003) and oxalate (330 versus 345 mg/day, P = 0.02) intake, as well as increased body mass index (28.5 versus 27.7 kg/m2, P = 0.001) and a history of hypertension (42% versus 34%, P = 0.001). A slightly lower dietary calcium intake (683 versus 711 mg/day, P = 0.04) was noted in case subjects versus control subjects, but interpretation was confounded by the study of prevalent rather than incident cases. Supplemental calcium intake >500 mg/day was inversely associated with stone occurrence., Conclusion: Multivariate risk factors for the occurrence of kidney stones in postmenopausal women include a history of hypertension, a low dietary intake of magnesium, and low use of calcium supplements.

Osteoporosis is a significant public health problem. Vertebral fractures are the most common fracture in patients with osteoporosis, occurring in approximately 750,000 cases each year. The fractures may cause acute or chronic pain, reduce the quality of life, and shorten life expectancy. Several medications are available that reduce the risk of fracture. Vertebroplasty and kyphoplasty (balloon-inflated expansion of collapsed vertebrae followed by injection of bone cement) may reduce or relieve pain in selected patients. Although surgery is rarely necessary for the management of osteoporotic vertebral fractures, it may be indicated for other reasons. No studies have been conducted to determine if the outcome of spinal fusion is different in patients with osteoporosis and, if it is, whether management of the patient's osteoporosis will improve the outcome.

Bisphosphonates are safe and effective agents for treatment and prevention of osteoporosis. Alendronate and risedronate are the best studied of all agents for osteoporosis in terms of efficacy and safety. They increase bone mass. In patients who have established osteoporosis, they reduce the risk of vertebral fractures. They are the only agents shown in prospective trials to reduce the risk of hip fractures and other nonvertebral fractures. They are approved by the US FDA for prevention of bone loss in recently menopausal women, for treatment of postmenopausal osteoporosis, and for management of glucocorticoid-induced bone loss. Other bisphosphonates (e.g., etidronate for oral use, pamidronate for intravenous infusion) are also available and can be used off-label for patients who cannot tolerate approved agents. Bisphosphonates combined with estrogen produce greater gains in bone mass compared with either agent used alone; whether there is a greater benefit of combination therapy on fracture risk is not clear. Combining a bisphosphonate with raloxifene or calcitonin is probably safe, although data on effectiveness are lacking.

Osteoporosis affects more than 28 million Americans. With the advent of accessible and affordable diagnostic studies, awareness and recognition of this disease by patients and clinicians are growing. Osteoporotic fractures of the spine and hip are costly and associated with significant morbidity and mortality. Over the past decade, a surge of new antiosteoporotic drugs have been labeled or are awaiting labeling by the U.S. Food and Drug Administration. One class of agents used to treat osteoporosis is the bisphosphonates, which inhibit bone resorption, cause an increase in bone mineral density and reduce the risk of future fractures caused by aging, estrogen deficiency and corticosteroid use. Overall, bisphosphonates have been shown to have a strong safety and tolerability profile.

The Bone Mass Measurement Act (BMMA) set forth regulations to provide for uniform coverage under Medicare Part B for bone mass measurements for services provided on or after July 1, 1998. The BMMA authorizes Medicare coverage of "medically necessary approved measurements" performed for a "qualified individual" who falls into at least one of five diagnostic categories: an estrogen-deficient woman at clinical risk for osteoporosis; an individual with vertebral abnormalities; an individual receiving long-term glucocorticoid (steroid) therapy; an individual with primary hyperparathyroidism; and an individual being monitored to assess the response to, or efficacy of, an approved osteoporosis drug therapy. Proper communication is essential for reimbursement. The tools for communication include Physician's Current Procedural Terminology (CPT), HCFA (Health Care Financing Administration) Common Procedure Coding System (HCPCS), the Medicare carrier's local Medical Review Policy (LMRP), and the International Classification of Diseases, ninth revision (ICD-9). This article reviews the new regulations and the tools for communication.

Biochemical markers of bone turnover have emerged as powerful tools to aid in managing osteoporosis. The newer bone markers have been intensively studied for more than a decade. As a result, we can now confidently report their clinical utility in assessing risk of rapid bone loss and fracture, and monitoring therapy in postmenopausal women with or at risk of osteoporosis. In this review, we will provide a comprehensive foundation for this utility. While there are still questions remaining to be answered, bone marker technology has matured to play an essential role in patient management. We will describe, in practical terms, how bone markers can be appropriately incorporated into clinical practice today.

Remodeling is essential for bone health. It begins with resorption of old bone by osteoclasts, followed by the formation of new bone by osteoblasts. Remodeling is coupled (formation is linked to resorption). After middle age or perhaps beginning earlier, bone loss occurs because resorption exceeds formation. This imbalance is accentuated by estrogen deficiency as well as by many diseases and conditions. Biochemical markers that reflect remodeling and can be measured in blood or urine include resorption markers (e.g., collagen cross-links) and formation markers (e.g., alkaline phosphatase). Bone markers exhibit substantial short-term and long-term fluctuations related to time of day, phase of the menstrual cycle, and season of the year, as well as diet, exercise, and anything else that alters bone remodeling. These biological factors, in addition to assay imprecision, produce significant intra- and interindividual variability in markers. Bone marker measurements are noninvasive, inexpensive, and can be repeated often. Unfortunately, most of the studies that provided insight on clinical situations did not focus on markers as a primary endpoint. Bone markers have been useful in clinical practice and have been helpful in understanding the pathogenesis of osteoporosis and the mechanism of action of therapies. In clinical trials, markers aid in selecting optimal dose and in understanding the time course of onset and resolution of treatment effect. Clinical questions that might be answered by bone markers include diagnosing osteoporosis, identifying "fast bone losers" and patients at high risk of fracture, selecting the best treatment for osteoporosis, and providing an early indication of the response to treatment. Additional information is needed to define specific situations and cut points to allow marker results to be used with confidence in making decisions about individual patients.

Bone densitometry has well-established usefulness in assessing fracture risk. Anyone with a condition that might reduce bone mass or accelerate bone loss should undergo testing, as should postmenopausal women and perimenopausal women who are undecided about starting estrogen replacement therapy. When stratifying a patient's risk of fracture, clinicians should consider not only BMD but also age, lifestyle, concurrent illness, and family history. Almost all patients with BMD in the osteoporotic range on densitometry should be considered for pharmacologic therapy, and so should many of those with values in the osteopenic range. Periodic retesting with bone densitometry is appropriate to monitor the progress of age-related bone loss and response to therapy. There are differences among skeletal sites used in BMD measurement, particularly regarding response to therapy. In addition, there are differences in calibration among densitometry machines, so whenever possible, serial studies should be done on the same machine and by the same technologist.

Several bisphosphonates are effective for preventing bone loss associated with estrogen deficiency, glucocorticoid treatment, and immobilization, and for at least partially reversing bone loss in patients with postmenopausal osteoporosis and steroid-induced osteoporosis. The most promising of these agents are etidronate, alendronate, risedronate, and ibandronate. These drugs should have an important role in the prevention and treatment of osteoporosis; however, more research is needed regarding optimal doses and regimens (continuous versus intermittent, oral versus parenteral), comparisons with other agents, and their use in combination with other agents.

Osteoporosis is a common and costly condition that can cause disability or death. Bone density testing permits identification of individuals who are at high risk of fracture. Adequate calcium, vitamin D, and weight-bearing exercise are important, but pharmacologic intervention is indicated and effective for increasing bone mass and decreasing fracture risk.

Purpose: To describe the clinical, histologic, and radiologic findings in patients with diabetic muscular infarction (DMI)., Materials and Methods: Descriptive case series of 3 patients with DMI and 22 previously reported cases (MEDLINE data base search) in the English literature are presented., Results: Diabetic muscular infarction is usually seen in patients with long-standing insulin-dependent diabetes and multiple end-organ microvascular complications. Two-thirds of patients with DMI are women, with a mean age at presentation of 39 +/- 12 years. The typical clinical presentation includes abrupt onset of thigh pain and tenderness. There is a palpable, painful mass, with swelling and induration of the surrounding tissue without systemic symptoms or signs. The painful lesion persists for weeks, occasionally with exacerbations of symptoms, then spontaneously resolves over several weeks to months. Recurrent episodes are reported in half of the patients. Muscles commonly affected are the vastus lateralis, thigh adductors, and biceps femoris; but calf muscles may be involved as well. Active pathologic changes in the muscle are more sensitively evaluated with T2-weighted sequences on magnetic resonance (MR) imaging, which shows high intensity in involved muscle. Histologic features of DMI consist of large areas of muscle necrosis and edema. Regenerating muscle fibers and lymphocytic interstitial infiltration may be present., Conclusion: Diabetic muscular infarction is a rare complication of diabetes mellitus. In most patients, the diagnosis can be made when the characteristic clinical presentation is combined with a typical MR imaging results. Muscle biopsy can be helpful in establishing the diagnosis of DMI, but histologic findings are not specific. Awareness of this syndrome plus MR imaging as the first diagnostic test should lead to the correct diagnosis and shorter hospitalization.

Low bone mass predicts future fracture risk as well as high cholesterol or high blood pressure can predict the risk of heart disease or stroke. Prevention of the first fracture should be a clinical goal. In patients without fractures, osteopenia and osteoporosis can be diagnosed based on the extent of reduction in bone mass below mean peak bone mass of young healthy individuals. As bone mass decreases, fracture risk increases exponentially. Clinical situations in which an assessment of bone mass and fracture risk affects therapeutic decisions include estrogen deficiency, vertebral abnormalities, radiographic osteopenia, asymptomatic primary hyperparathyroidism, and long-term corticosteroid therapy. Serial measurements can also be used to monitor the effects of osteoporosis treatments. The appropriate technique and skeletal site for bone mass measurements should be chosen based on the patient's circumstances and the precision of measurement. A clinical interpretation can enhance the value of computer-generated bone mass measurement reports and improve decision making.

Problem Considered: Reproducibility is only one dimension of test quality to be considered when evaluating the utility of a test or deciding to perform a test at or near the point of care., Methods: Personal experience and review of the literature., Results: Hemoglobin A1c and bedside glucose measurements are cited as examples in which a clinician may weigh the importance of precision differently. These examples are used to point out how precision should be considered in evaluating alternate site testing methodology., Conclusions: The importance of analytic precision to the clinician, and whether precision can be compromised for improvement of another dimension of test quality, depends on the context in which the result of the test is to be used. In addition to the purpose of the test, the level of precision required also depends on the patient population, the particular application of the test, and how the clinician interprets the test. Clinically relevant goals for test accuracy must be individualized for each test and application. Precision may be sacrificed for lower cost, increased availability, or faster turnaround time. Collaboration between laboratorians and clinicians is essential for optimal utilization of laboratory services.

Several bisphosphonates appear to be effective for preventing bone loss associated with estrogen deficiency, glucocorticoid treatment, and immobilization and for partially reversing bone loss in patients with postmenopausal osteoporosis and steroid-induced osteoporosis. The most promising of these agents are etidronate, alendronate, tiludronate, and risedronate. These agents should have an important role in prevention and treatment of osteoporosis; however, more research is needed regarding optimal doses and regimens (continuous versus intermittent), comparisons with other agents, and use in combination with other agents.

Persons at increased risk for osteoporotic fracture can be identified by clinical assessment and bone-density measurements. General measures (adequate amounts of calcium and vitamin D, along with an active lifestyle) can slow the rate of bone loss and should be recommended for all patients. Estrogen and parenteral salmon calcitonin are approved by the Food and Drug Administration for treatment of osteoporosis; these agents prevent bone loss in most patients and produce modest increases in bone mass, even in patients with advanced disease. Newer agents, such as bisphosphonates, provide additional therapeutic options.

Purpose: To determine the effect of long-term intermittent cyclic etidronate treatment on spinal bone density and vertebral fracture rates., Patients and Methods: Postmenopausal osteoporotic women (n = 423) were randomized initially into a 2-year, double-blind, multicenter study; it was extended to a third year of blinded treatment followed by open-label treatment: 357 patients continued treatment in Year 3 (305 receiving blinded therapy and 52 receiving calcium supplementation) and 277 in Year 4. During Years 1 through 3, patients received double-blind treatment with phosphate (1.0 g) or placebo twice daily for 3 days, etidronate (400 mg) or placebo daily for 14 days, and calcium (500 mg) daily for the remainder of each 91-day treatment cycle. During Year 4, open-label intermittent cyclic etidronate therapy (without preceding phosphate) was administered to all patients. Spinal bone density and vertebral fracture rates were the main outcome measures., Results: During Year 3, etidronate therapy maintained the significant increases in spinal bone mineral density of the first 2 years. Over the 3-year period, proximal femur bone density increased in etidronate-treated patients. Etidronate therapy for 3 years significantly decreased the vertebral fracture rate in patients at higher risk for fracture (low spinal bone density and three or more vertebral fractures at study entry), as compared with nonetidronate treatment (228 versus 412 fractures per 1,000 patient-years, respectively; p < 0.05). After 1 year of open-label treatment, patients previously treated with etidronate maintained bone mass, and vertebral fracture rates in all groups were lower than in any other study period. There were no apparent serious adverse effects., Conclusions: Three years of intermittent cyclic etidronate therapy produced significant increases in spinal and hip bone density, with a significant reduction in vertebral fracture rates in patients at higher fracture risk. Maintenance of bone mass and low fracture rate were observed when etidronate was continued for an additional year.

The results of transsphenoidal adenomectomy for growth hormone (GH)-secreting pituitary adenomas in acromegaly performed over a 17-year period were analyzed retrospectively to determine which preoperative factors significantly influenced the long-term surgical outcome. These variables were then used to develop a logistic regression model to determine the probability of surgical failure. The series consisted of 103 patients. Long-term follow-up study (mean duration 102 +/- 64 months) was performed to derive outcome analysis and determinants of failure. Surgical control was defined as a long-term postoperative serum basal GH level of less than 5 micrograms/liter, a long-term postoperative serum somatomedin C (SM-C) level of less than 2.2 U/ml, and a favorable clinical response. Eighteen (17.5%) patients did not meet these criteria. The overall control rate by the GH criteria was 81.3% and by the SM-C criteria 76.2%. By multivariate logistic regression analysis, tumor stage was the strongest predictor of outcome (p < 0.05). The preoperative GH level, tumor grade, and preoperative SM-C level were significant univariate predictors (p < 0.05). There were statistically significant differences in mean preoperative GH and SM-C levels (p < 0.05, t-test) and tumor stage (p < 0.05, chi-squared test) between patients whose acromegaly was controlled by surgery and those whose acromegaly was not. Furthermore, estimates were derived of the probability of surgical failure based on preoperative GH level, preoperative SM-C level, and tumor grade and stage. The authors believe these findings will enhance clinical decision-making for neurosurgeons considering transsphenoidal microsurgery in patients with acromegaly.

Bisphosphonates are agents that are potentially useful for treatment of osteoporosis. They are antiresorptive agents, increasing bone mass by decreasing the frequency of osteoclast activation or the depth of osteoclast resorption, or both. Intermittent cyclical therapy with etidronate has been shown to be effective for postmenopausal osteoporosis in two controlled studies. Several second- and third- generation bisphosphonates are undergoing active clinical trials.

Ten patients were studied before and after autologous adrenal medullary transplantation to the central nervous system for Parkinson's disease to determine if the presence of new catecholamine-producing tissue near the hypothalamus would alter hypothalamic or pituitary function, mineralocorticoid levels, or catecholamine production. No clinically apparent ill effects occurred. Changes in endocrine function were largely short-term and transient: at 7-10 days after surgery, urinary catecholamine levels were significantly increased, PRL levels were significantly elevated despite markedly increased serum dopamine levels, and gonadal steroid levels (estradiol and testosterone) were significantly lower despite unchanged basal and stimulated levels of gonadotropins. Dehydroepiandrosterone sulfate was significantly reduced at 7-10 days after surgery and remained low at 3-6 months. Other changes at 3-6 months after surgery included increased stimulated corticotropin levels and reduced serum aldosterone response to upright posture. The changes at 7-10 days were probably due to stress or unilateral adrenalectomy or both; the changes at 3-6 months were likely due to unilateral adrenalectomy. We conclude that unilateral adrenalectomy and autologous adrenal medullary transplantation to the central nervous system does not produce clinically important changes in endocrine function; however, possible adverse consequences of long-term reduction of dehydroepiandrosterone sulfate levels cannot be excluded.

Background: To determine the effects of etidronate (a bisphosphonate that inhibits osteoclast-mediated bone resorption) in the treatment of postmenopausal osteoporosis, we conducted a prospective, two-year, double-blind, placebo-controlled, multicenter study in 429 women who had one to four vertebral compression fractures plus radiographic evidence of osteopenia., Methods: The patients were randomly assigned to treatment with phosphate (1.0 g) or placebo twice daily on days 1 through 3, etidronate (400 mg) or placebo daily on days 4 through 17, and supplemental calcium (500 mg) daily on days 18 through 91 (group 1, placebo and placebo; group 2, phosphate and placebo; group 3, placebo and etidronate; and group 4, phosphate and etidronate). The treatment cycles were repeated eight times. The bone density of the spine was measured by dual-photon absorptiometry, and the rates of new vertebral fractures were determined from sequential radiographs., Results: After two years, the patients receiving etidronate (groups 3 and 4) had significant increases in their mean (+/- SE) spinal bone density (4.2 +/- 0.8 percent and 5.2 +/- 0.7 percent, respectively; P less than 0.017). The rate of new vertebral fractures was reduced by half in the etidronate-treated patients (groups 3 and 4 combined) as compared with the patients who did not receive etidronate (groups 1 and 2 combined) (29.5 vs. 62.9 fractures per 1000 patient-years; P = 0.043); the effect of treatment was most striking in the subgroup of patients with the lowest spinal bone mineral density at base line, in whom fracture rates were reduced by two thirds (42.3 vs. 132.7 fractures per 1000 patient-years; P = 0.004). The addition of phosphate provided no apparent benefit. There were no significant adverse effects of treatment., Conclusions: Intermittent cyclical therapy with etidronate for two years significantly increases spinal bone mass and reduces the incidence of new vertebral fractures in women with postmenopausal osteoporosis.