Individuals with rheumatoid arthritis (RA) continually fall short of treatment targets using standard drug therapies alone. There is growing evidence that emphasizing physical and mental wellness is equally crucial for improving functioning among people with RA. The purpose of this formative study is to examine the feasibility of offering the wellness-based intervention ("KickStart30") in patients with RA. Thirteen individuals with RA on targeted immune modulators (a biologic or JAK inhibitor) enrolled in the KickStart30 program. Participants completed self-report measures of RA-specific disability (eg, pain) and other functional areas (eg, mood) in a pre- versus post- intervention design. Paired samples t-tests (and Related-Samples Wilcoxon Signed Rank Tests for non-normal distributions) detected statistically significant results for 10 of 12 measures, including reductions in pain (M = 4.54 to M = 3.54; p = .025; BPI), functional disability (M = 0.94 to M = 0.73, p = .032; HAQ-II), cognitive and physical dysfunction (M = 25.46 to M = 13.54, p < .001; CPFQ), depressive symptoms (M = 9.31 to M = 5.54, p = .003; PHQ-9), anxiety (M = 5.69 to M = 3.23, p = .005; GAD-7), insomnia (M = 11.62 to M = 17.32, p = .007; Note: higher scores on the SCI indicate less insomnia), stress-related eating (M = 75.46 to M = 84.54, p = .021; Note: higher scores on the EADES indicate less stress-related eating), along with significant increases in mindfulness (M = 62.54 to M = 67.85, p = .040; MAAS), mental wellness (M = 4.46 to M = 5.69; HERO), and well-being (M-d = 8.00 to M-d = 5.00, p = .004; WHO-5). All significant measures had medium to large effect sizes (Cohen's d). The study gives preliminary support for the possibility that the adjunct intervention may have an effect.

This expert opinion article explores the strategy of adopting a holistic approach to the management of rheumatoid arthritis (RA) by incorporating the wellness practices of exercise, optimised sleep, optimised nutrition, mindfulness, social connectedness and positive emotions into the management plan. The aim is to attain optimal health for each patient beyond that achievable by limiting disease management to pharmacological treatment to attain the lowest achievable composite scores of disease activity, as recommended with the current treat-to-target approach, and addressing the recent recognition of pain control as a key patient-reported outcome. Incorporating wellness practices into a busy clinical setting requires creativity and customisation based on the individual practice setting and the individual needs of each patient. Such practices can help people living with RA to achieve optimum wellness through the introduction of measures—according to individual need—designed to improve the aspects of life most impacted for that person, thereby complementing treat-to-target and pain control strategies with pharmacological agents. Clinicians must consider wellness practices in addition to treat-to-target pharmacological agents for the holistic management of people with RA.

The 2020 American Association of Clinical Endocrinologists guidelines for assessing osteoporosis among postmenopausal women stratified postmenopausal women with osteoporosis to "high" and "very-high" fracture risk categories and recommended anabolic agents as initial therapy followed by an antiresorptive agent. Switching the order can blunt the effect of anabolic agents, and failing to follow with an antiresorptive can lead to loss of bone generated by the anabolic agent. It would be helpful to understand the real-world prescribing patterns of anabolic agents. Using the 2010-2015 Medicare 100% osteoporosis database, we assessed patient profiles, teriparatide prescribers, persistence of teriparatide therapy, and antiresorptive agent use after teriparatide discontinuation among elderly women who initiated teriparatide from 2011 to 2013. This study included 14,786 patients. In the year before teriparatide initiation, 30.0% of them had a fracture, 67.6% had a dual energy x-ray absorptiometry scan, 74.4% had a diagnosis of osteoporosis, and 47.9% used antiresorptive agents (non-naive teriparatide users). Among those who had fractures, 49.4% initiated teriparatide within 3 months postfracture. Teriparatide was prescribed for 37% of users by primary care doctors, 19% by rheumatologists, 13% by endocrinologists, and 7.0% by orthopedists. Median time of teriparatide use was 7.2 months. After teriparatide discontinuation, 40.8% switched to antiresorptive agents (31.9% among naive teriparatide users, 50.5% among non-naive users). Among switchers, 42.5% switched within 60 days, 50.5% switched to denosumab, and 31.6% switched to oral bisphosphonates. This study of real-world prescribing data found that about half of teriparatide users switched from an antiresorptive agent, and less than half switched to antiresorptive agents after teriparatide discontinuation. Persistence of teriparatide use was suboptimal. In the management of postmenopausal osteoporosis, increasing the persistence of teriparatide use and improving the appropriate treatment sequence of anabolic and antiresorptive drugs are critical to maximizing gains in bone mass, providing the greatest protection against fractures. (c) 2021 American Society for Bone and Mineral Research (ASBMR).

Assessment of bone mineral density (BMD) by dual-energy x-ray absorptiometry (DXA) plays a vital role in the diagnosis of osteoporosis and in monitoring a patient's response to drug therapy. This commentary will discuss controversies surrounding the use of DXA for screening and monitoring of BMD in women.

Editor's Note: In this issue of the JBMR, we introduce a new feature called Viewpoints. The intent of Viewpoint articles is to provide rapid, critical commentaries, generally reflecting differing perspectives, on pressing topics arising in the bone field that the editors believe deserve immediate discussion and dissemination. Viewpoints will be concise, focused opinions of new original studies or other issues that are deemed to have immediate impact on understanding bone and mineral biology or clinical practice. The inaugural Viewpoint articles, which appear in this issue, address the recent controversy surrounding the proposed frequency for performing bone mineral density in older postmenopausal women. A strong correlation between skeletal mechanical strength and BMD measured by DXA1; A robust relationship between fracture risk and BMD measured by DXA in clinical trials and epidemiological studies2; The primacy of DXA in the 1994 World Health Organization (WHO) classification of skeletal health into normal, osteopenic, or osteoporotic categories3; DXA's pivotal role in identifying eligible subjects in all registration trials for medications now approved to treat osteoporosis4; Excellent accuracy and precision of DXA5; and Low patient exposure to ionizing irradiation with DXA.6 The WHO's Fracture Risk Assessment Tool (FRAX) algorithm employs femoral neck BMD by DXA as the only validated bone density measurement.7 Serial BMD performed by DXA is used to monitor the course of patients who are treated with U.S. Food and Drug Administration (FDA)-approved drugs for osteoporosis.8 In fact, DXA is the only measurement technology recognized by the Center for Medicare and Medicaid Services (CMS) in the United States for monitoring therapy with serial BMD measurements.9 DXA is also the technology recommended by the U.S. Surgeon General10 and the U.S. Preventive Services Task Force (USPSTF)11 for population screening. Osteoporosis screening strategies with BMD testing are cost-effective.12 Increases in BMD testing rates in appropriately selected patients have been proven to reduce the incidence of fractures and reduce healthcare costs, including the expenses associated with BMD testing and treatment.13, 14 More sophisticated technologies may come along, in time, that can be used in clinical practice to measure skeletal features not currently identified by DXA, such as bone strength, true volumetric density (mg/cm3), dynamic features of bone remodeling, and skeletal microarchitecture. Currently, however, there is no other skeletal health assessment technology that provides as much clinical information as DXA for screening, identification of patients at high risk for fracture, and monitoring patients, whether or not they are on drug therapy. The recent study by Gourlay and colleagues15 from the Study of Osteoporotic Fractures (SOF) has raised questions about intervals between BMD measurements in older postmenopausal women. The study cohort of 4957 women was a subset of 8514 women in SOF who had BMD testing by DXA. Women in SOF were excluded from this analysis if there was a diagnosis of osteoporosis (defined as T-score ≤ −2.50 at the femoral neck or total femur), treatment for osteoporosis, a past history of a hip or clinical vertebral fracture, or a follow-up DXA study was not available for review. All women studied were ambulatory with normal BMD (T-score −1.00 or higher at the femoral neck or total hip) or osteopenia (T-score between −1.00 and −2.50 at the femoral neck or total hip); age was ≥67 years and >99% were white. The primary outcome measure was the estimated interval for 10% of participants to make the transition from normal BMD or osteopenia at baseline to osteoporosis, before a hip or clinical vertebral fracture occurred or before treatment for osteoporosis was started. As would be expected, the authors found that a higher baseline BMD was associated with a longer time to develop osteoporosis and that women with normal bone density at the age of 67 years were unlikely to have subsequent rapid bone loss. In women with normal baseline BMD, the mean adjusted interval for 10% of study participants to develop osteoporosis was 16.8 years (95% confidence interval [CI], 11.5–24.6). In individuals aged 67 years who had low baseline BMD values, the time to develop osteoporosis was shortened, with participants having “advanced osteopenia” (baseline T-score between −2.00 and −2.50) having an adjusted interval of only 1.1 years (95% CI, 1.0–1.3) for 10% to develop osteoporosis. The findings are consistent with other studies showing an age-related bone loss of about 1% per year in women with similar characteristics.16 Based on such data, a recommendation for extended BMD retesting intervals in older white women with favorable baseline BMD values and low risk of rapid bone loss or fracture is reasonable. The authors correctly identified limitations of the study that preclude its applicability to a wider patient population. The study cohort was restricted to preselected women ≥67 years of age and did not include men or younger postmenopausal women. It is particularly important to note that women in their early postmenopausal years are likely to experience accelerated bone loss that may require short testing intervals (eg, 1–2 years) to assess. Also excluded from the trial were nearly 50% of the SOF study participants who had a previous diagnosis of osteoporosis (based on a prior hip or clinical vertebral fracture or densitometric evidence of osteoporosis) or who were already on treatment for osteoporosis. Other limitations to the trial were not noted by the authors. Only clinical vertebral fractures were considered in the analysis, although undiagnosed morphometric vertebral fractures are common in patients with densitometric evidence of osteopenia and are associated with high morbidity.17 In a prospective cohort study of 671 postmenopausal women undergoing periodic spine imaging, 48% of vertebral fractures were found in women with T-scores between −1.0 and −2.5. With a morphometric vertebral fracture, they would be reclassified as having a clinical diagnosis of osteoporosis.18 Many of these patients would not have been identified in the study of Gourlay and colleagues.15 In making treatment decisions in clinical practice, it is imperative to consider risk factors for fracture in addition to the femoral neck and total hip T-score. Gourlay and colleagues, for example, did not measure lumbar spine BMD. Low lumbar spine BMD is associated with increased fracture risk at all skeletal sites.19 Moreover, lumbar spine T-score may be ≤ −2.5 even if the femoral neck or total hip T-score is > −2.5. Without tracking lumbar spine BMD, Gourlay and colleagues may have underestimated the number of individuals who progressed to osteoporosis during the study. Most importantly, with its singular focus on BMD, the study did not capture those patients with osteopenia who by FRAX fracture risk assessment would have been at high risk for fracture and therefore warrant drug therapy. Not unexpectedly, the study by Gourlay and colleagues15 generated considerable media attention, suggesting that DXA was an expensive test that was overused and abused by physicians,20, 21 and that Medicare will save money if fewer DXA studies are performed.22 In reality, overtesting with DXA is not a problem. The real problem is that far too few patients are being screened for osteoporosis. The annual Medicare Part B testing rate for women 65 years of age and older is only 14%, with a decline in the annual rate of testing in 2010.23 A recent Medicare claims analysis by King and Fiorentino23 during the 7-year period from 2002 to 2008 demonstrated that 48% of elderly women had not had a single DXA study. Only 25% had one test, 15% had two tests, 8% had three tests, 2% had four tests, and <1% had five or more tests. Importantly, the claims data also included women already diagnosed with osteoporosis and those on drug therapy, patients who were excluded from the study by Gourlay and colleagues.15 Although concerns have been raised that some screening prevention programs for other chronic diseases do not result in healthcare savings,24 that is not the case for BMD testing in appropriately selected patients. The experience of healthcare systems suggests that increases in BMD testing reduce fracture rates and save money. A 5-year observational study evaluated the clinical and fiscal outcomes of the Geisinger Health System Osteoporosis Disease Management Program from 1996 to 2000.14 It was found that implementation of osteoporosis guidelines that included increases in BMD testing and treatment was associated with a significant decrease in the age-adjusted incidence of hip fractures and an estimated $7.8 million reduction in healthcare costs during this 5-year period. At Kaiser Southern California, an osteoporosis disease management program (“Healthy Bones Program”) was fully implemented in 2002, with a goal of reducing hip fractures by increasing BMD testing rates and treatment in patients at high risk of hip fracture.25, 26 It was estimated that in 2006, 935 hip fractures, with an average cost of $33,000 each, were prevented, resulting in savings of over $30.8 million for Kaiser.13 Multiple osteoporosis screening strategies have been found to be clinically effective, and cost-effective as well.12, 27, 28 Osteoporosis is a major public health concern.10 More than 200 million women and men are estimated to have osteoporosis worldwide, including about 10 million Americans.29, 30 There are about 2 million osteoporotic fractures each year in the United States, resulting in over 432,000 hospital admissions, almost 2.5 million medical office visits, and increased risk of disability and death,31, 32 with healthcare costs exceeding $18 billion.33 Despite the availability of DXA to diagnose osteoporosis and the use of FRAX to assess fracture risk, osteoporosis remains a disease that is underdiagnosed.34 Although FDA-approved therapies that are proven to reduce fracture risk are widely available, the disease is still, in 2012, undertreated.35-40 Recent declines in Medicare DXA reimbursement in the United States to levels that are below the cost of providing the procedure have been associated with a reduction in BMD testing.23 Failure to appreciate the limitations of the study reported by Gourlay and colleagues15 may have adverse consequences that further reduce BMD testing due to a negative impact on policy formulated by CMS, legislators, and insurers. This negative scenario could result in fewer patients tested for osteoporosis, fewer patients treated, more fractures, and higher healthcare costs.41 More BMD testing, not less, is needed to screen for osteoporosis. This is good clinical practice, cost-effective, and will reduce the burden of osteoporotic fractures. Current evidence-based guidelines for BMD testing should be followed. The National Osteoporosis Foundation,30 the International Society for Clinical Densitometry (ISCD),42 and the USPSTF11 all recommend BMD testing for women ≥65 years of age and for younger women who may be at high risk for fracture according to prespecified parameters. Monitoring for treatment effect is recommended 1 to 2 years after starting or changing therapy,30, 42 with consideration of longer testing intervals once a favorable treatment effect is confirmed. The ISCD Official Positions state that intervals between BMD testing should be determined according to each patient's clinical status42; the USPSTF suggests screening intervals of at least 2 years in women with normal baseline BMD.11 Both of these recommendations are consistent with the findings of Gourlay and colleagues.15 When screening shows that BMD is normal or slightly low in women age ≥67 years, and there are no clinical risk factors for fracture or rapid bone loss, a long interval until repeat testing is appropriate. For younger patients, for those with BMD values substantially below normal, for those with prior fracture or clinical risk factors for fracture, and for those started on osteoporosis drug therapy, a repeat BMD test should be done after a much shorter time interval. EML has received grant support from Amgen, Eli Lilly, Novartis, Merck, Warner Chilcott, and Glaxo-SmithKline; has served on advisory boards for Amgen, Eli Lilly, Novartis, and Merck; has been a consultant to Glaxo-SmithKline; and has received speaking fees from Amgen, Eli Lilly, Novartis, and Warner Chilcott. AJL has served on advisory boards for Amgen, Genentech, and Lilly; has received speaking fees from Amgen, Genentech, Lilly, Novartis, and Roche/Glaxo-SmithKline; has been a faculty member, committee member, and ex-officio Board member for the International Society for Clinical Densitometry (ISCD); and has served as President of ISCD and a Board member for the past 3 years. PDM has received grant support from Proctor & Gamble Pharmaceuticals, Sanofi-Aventis, Roche, Eli Lilly, Merck, Novartis, Amgen, Takeda, Radius, and GE Healthcare; has served on advisory boards for and has also been a consultant to Proctor & Gamble Pharmaceuticals, Merck, Eli Lilly, Amgen, Novartis, Roche, GlaxoSmithKline, and Baxter; has been a consultant to Wright; has received speaking fees from Proctor & Gamble Pharmaceuticals, Novartis, and Roche; and has served as Editor-in-Chief of the Journal of Clinical Densitometry. JPB has served as a consultant for Eli Lilly, Merck, Radius, and Amgen, and has received speaking fees from Eli Lilly, Amgen, and Novartis. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

OBJECTIVE:To evaluate the efficacy and safety of treatment with ocrelizumab plus methotrexate (MTX) in patients with active rheumatoid arthritis (RA) and an inadequate response to MTX.METHODS:STAGE was a phase III randomized, double-blind, parallel-group international study to evaluate the safety and efficacy of ocrelizumab compared with placebo in patients with active RA continuing MTX treatment. Patients receiving stable doses of MTX were randomized to receive 2 infusions of placebo (n = 320), ocrelizumab 200 mg (n = 343), or ocrelizumab 500 mg (n = 343) on days 1 and 15 as well as weeks 24 and 26. Coprimary end points were the proportion of patients with an American College of Rheumatology 20% improvement criteria (ACR20) response at weeks 24 and 48. Secondary end points included the change from baseline in the modified Sharp/van der Heijde score (SHS) and the ACR50/70 responses.RESULTS:The ACR20 response rates were 35.7% in the placebo group, 56.9% in the ocrelizumab 200 mg group, and 54.5% in the ocrelizumab 500 mg group at 24 weeks, and 27.6%, 58.3%, and 62.1%, respectively, at 48 weeks (P < 0.0001 versus placebo for each dose at both time points). At week 48, both of the ocrelizumab doses improved the ACR50 and ACR70 response rates 3-fold as compared with placebo and showed a statistically significant (P < 0.0001) reduction in joint damage progression relative to placebo (mean change in SHS reduced by 85% and 100% for the 200-mg and 500-mg doses, respectively). Rates of serious infection were comparable in the placebo (3.48 per 100 patient-years) and ocrelizumab 200 mg (3.54 per 100 patient-years) groups but were elevated in the ocrelizumab 500 mg group (8.66 per 100 patient-years).CONCLUSION:With both ocrelizumab doses, the primary end point was met, and the signs and symptoms of RA were significantly improved at weeks 24 and 48. Ocrelizumab also significantly inhibited the progression of joint damage. A higher rate of serious infections was observed with 500 mg of ocrelizumab as compared with ocrelizumab 200 mg or placebo.

Although a variety of medications are effective for the treatment of postmenopausal osteoporosis, there is concern that long-term use may incur side effects. Consequently, some have proposed discontinuing or temporarily suspending treatment after a defined period of time. As the benefits of fracture risk reduction may recede during this "drug holiday", the clinician may be faced with deciding when to resume therapy (and with which agent) while avoiding the possible cumulative risk of side effects. This article summarizes data regarding length of treatment and the effects of cessation of treatment on bone density, bone turnover markers, and fracture risk.

In the United States, Medicare gradually reduced payments for central dual-energy X-ray absorptiometry (DXA) performed at physician offices (or other nonhospital settings) from an average of $139 in 2006 to about $82 in 2007 and 2008 and $72 in 2009. Reimbursement for hospital outpatient DXA service was unchanged. We investigated the utilization of hip and spine (central) DXA in the Medicare population before and after the reduction. We identified individuals from the national 5% random sample of Medicare beneficiaries who were >65 years of age and enrolled in Medicare Parts A and B but not in a Medicare Advantage plan from 2002 through 2009. For each calendar year, we calculated the proportion of beneficiaries who submitted claims for DXA, the proportions of DXAs performed in hospitals and in physician offices and the number of physician office-based practices that discontinued or started to provide DXA services. From 2002 to 2006, the proportion of beneficiaries who had at least one central DXA increased from 7.9% to 9.6% at an annual increase of 0.4% and from 2006 to 2009, the annual increase dropped to 0.1%. The number of DXAs performed in physician offices dropped from 1,643,720 (69% of 2,363,500 total DXAs) in 2006 to 1,534,240 (66% of 2,338,240) in 2009. This decline was offset by an increase in the number of DXAs performed in hospitals, which increased from 719,780 (31%) in 2006 to 804,000 (34%) in 2009. Among physician office-based practices, more practices initiated than discontinued DXA service each year from 2002 to 2006. However, the trend was reversed since 2007 such that in 2009, 1876 practices discontinued and only 1394 initiated DXA service. The reduction in DXA reimbursement was associated with a decrease in the number of DXAs performed in physician offices and fewer physician offices that provided DXA services. (c) 2012 American Society for Bone and Mineral Research.

In January 2007, in the United States (US), Medicare initiated a series of cuts to reimbursement for dual-energy X-ray absorptiometry (DXA) services performed in the nonfacility setting that by January 2010 reduced payments for these services by more than 60% compared with 2006 levels. The objectives of this study were to determine if a temporal association exists between Medicare Physician Fee Schedule changes in office-based DXA reimbursement and attendance at educational conferences for osteoporosis, physicians' perceptions of changes in their medical practices, or national trends in retail prescription medications for osteoporosis in those aged 65 and older. Compared with the 2 yr before the decline in Medicare reimbursement for DXA (2005-2006), attendance at educational meetings for osteoporosis in the US declined in the 2 yr after these cuts (2007-2008) by 6%; declines in attendance were only present in meetings selective for bone densitometry. Survey participants reported changes in DXA services with approximately one-third indicating that they had either decreased the number of DXAs they performed or declined service contracts or hardware/software updates compared with 2005-2006. The number of retail prescriptions for Food and Drug Administration-approved osteoporosis drugs (excluding estrogen compounds and raloxifene) in the age 65 and older population increased by 5.5% in the time period 2007-2008 compared with 2005-2006. However, in the last year of the study (2008), total retail prescriptions for these drugs experienced for the first time over the interval of the study, a decline (1.4%) compared with the previous year. This occurred despite a 2.6% increase in the US population age 65 and older. In conclusion, there were temporal associations noted between Medicare cuts in DXA payments in attendance at educational conferences for bone densitometry, self-report of office-based provision of DXA services in the US, and retail prescriptions for osteoporosis therapies.

Osteoporosis is a common skeletal disease with serious clinical consequences because of fractures. Despite the availability of clinical tools to diagnose osteoporosis and assess fracture risk, and drugs proven to reduce fracture risk, it remains a disease that is underdiagnosed and undertreated. When treatment is started, it is commonly not taken correctly or long enough to be effective. Recent advances in understanding of the regulators and mediators of bone remodeling have led to new therapeutic targets and the development of drugs that may offer advantages over current agents in reducing the burden of osteoporotic fractures. Many genetic factors that play a role in the pathogenesis of osteoporosis and metabolic bone disease have now been identified. At the 2009 Santa Fe Bone Symposium, held in Santa Fe, New Mexico, USA, the links between advances in genetics, basic bone science, recent clinical trials, and new and emerging therapeutic agents were presented and explored. Socioeconomic challenges and opportunities in the care of osteoporosis were discussed. This is a collection of medical essays based on key presentations at the 2009 Santa Fe Bone Symposium.

E. Michael Lewiecki,* John P. Bilezikian, Andrew J. Laster, Paul D. Miller, Robert R. Recker, R. Graham G. Russell, and Michael P. Whyte New Mexico Clinical Research & Osteoporosis Center, Albuquerque, NM, USA; Columbia University College of Physicians and Surgeons, NYC, NY, USA; Arthritis and Osteoporosis Consultants of the Carolinas, Charlotte, NC, USA; Colorado Center for Bone Research, Lakewood, CO, USA; Creighton University School of Medicine, Omaha, NE, USA; The Botnar Research Centre, University of Oxford, Oxford, UK; and Washington University School of Medicine, St. Louis, MO, USA

Low trauma fractures are the cardinal manifestation of osteoporosis. Their occurrence supersedes bone mineral density in deciding whether specific therapy is warranted. We therefore disagree with the notion that a densitometric threshold for treatment should be applied to patients over age 50 who suffer low trauma distal radius fracture.

Osteoporosis is a common disease with serious medical and economic consequences. Despite great efforts to educate healthcare professionals and the public, it remains underdiagnosed and undertreated. BMD testing by DXA is an extraordinarily useful clinical tool for assessment of fracture risk and to diagnose osteoporosis before the first fracture occurs. DXA is the only technology for measuring BMD that can be used with FRAX, the World Health Organization fracture risk assessment algorithm that is becoming widely used throughout the world. Several organizations recommend serial DXA testing for monitoring pharmacologic therapy of osteoporosis.1-3 The utility of BMD testing to monitor therapy was questioned almost a decade ago when the concept of “regression to the mean” was raised.4 Although this concept has relevance at a population level, it was subsequently refuted as misleading and irrelevant to the clinical management of individual patients.5, 6 A study published recently in BMJ by Bell et al.7 raises the question anew. Despite the title, “Value of Routine Monitoring of Bone Mineral Density after Starting Bisphosphonate Treatment: Secondary Analysis of Trial Data,” the authors conclude that monitoring BMD “in postmenopausal women in the first three years after starting treatment with a potent bisphosphonate is unnecessary and may be misleading.” The authors go on to state that “routine monitoring should be avoided in this early period.” These conclusions are based on a secondary analysis of pooled data from the two arms of the Fracture Intervention Trial (FIT) in which postmenopausal women with low BMD were randomized to alendronate or placebo.8, 9 They conclude that using BMD to monitor response to treatment with alendronate was of no value because (1) >97% of the patients on treatment ultimately showed an increase in BMD and (2) the within-subject variability was considerable. Several of the same authors used a similar approach in a post hoc analysis of the Perindopril Protection Against Recurrent Stroke Study (PROGRESS)10 to conclude that monitoring the initial blood pressure response after perindopril (an angiotensin-converting enzyme inhibitor) therapy was unnecessary.11 The purpose of this commentary is to address issues raised by Bell et al. and to place the need for BMD monitoring into an appropriate clinical context. Whereas we applaud all efforts to apply the best available medical evidence to clinical decision-making, the validity and applicability of evidence should be closely scrutinized before making recommendations.12 The conclusion of the recent BMJ article, that monitoring therapy with BMD testing is unnecessary, rests on four assumptions: (1) the goal of monitoring is to document effectiveness by showing an increase in BMD, (2) the increase in BMD in virtually all treated subjects in FIT can be expected to occur in patients in clinical practice, (3) the response to one bisphosphonate in a clinical trial is indicative of the response to all bisphosphonates in clinical practice, and (4) within-person variability obscures detection of the BMD response to treatment. We believe that all of these assumptions are incorrect or unfounded as described below. The goal of therapy for osteoporosis is to reduce the risk of fractures. Although, in untreated individuals, low BMD is a good predictor of fracture risk,13 and there is a statistically significant relationship between BMD increase in response to therapy and reduction in fracture risk,14 the relationship between the increase in BMD from therapy and reduction of fracture risk is not strong and probably not linear.15 Patients on treatment for osteoporosis whose BMD remains stable or increases seem to benefit equally, at least in regard to the rates of new vertebral fractures.16-18 It is therefore not necessary to monitor BMD to determine how much a patient's BMD increased on treatment. However, in these same analyses, patients on treatment whose BMD decreased had higher rates of fractures compared with those on treatment whose BMD was stable or increased. (Bell et al. misinterpreted one of the studies they cited; they suggest that fracture risk reduction was seen in patients who lost BMD on alendronate, but that study actually showed no significant reduction in fracture risk for patients on treatment whose BMD decreased by the least significant change [LSC] or greater.18) Thus, there is clearly a need to identify patients whose BMD decreases despite treatment. The assumption that virtually all patients who are treated with alendronate would show a significant increase in BMD, as seen in this analysis of the FIT data, does not apply to patients in clinical practice. Patients in clinical trials are different from patients that we treat in the “real world.” Dowd et al.19 matched key characteristics of the patients they were treating in their osteoporosis clinic with the entry criteria for four different osteoporosis clinical trials. In the best case scenario, 80% of patients being treated in their practice would have been excluded from participation in one of the trials, whereas in the worst case scenario, 97% would have been excluded from another (too old, too young, too many medications, etc.). In FIT, patients were excluded if they had dyspepsia requiring ongoing treatment, prior peptic ulcer disease, or “major medical problems that would likely preclude participation for three years.”8 In the real world, such patients are not denied treatment for osteoporosis. Compared with patients in the “real world,” subjects who are enrolled in clinical trials are more likely to take their medicine regularly and correctly and to persist with treatment. Trial subjects probably do better with other lifestyle factors such as calcium, vitamin D, and exercise. In FIT, >85% of subjects were still taking their study drug at the end of the trial; 96% of those still taking their study drug took it at least 75% of the time. In contrast, a study of patients in clinical practice showed that <45% were compliant with prescription refills and only 20% were continuing treatment with bisphosphonates after 24 mo.20 Patients in FIT who had significant bone loss in the lumbar spine or total hip (≥8% over 1 yr, ≥10% over 2 yr, ≥12% over 3 yr) were dropped from the trial9 and so were not included in the analysis of Bell et al. Patients in clinical trials are supplemented with calcium and vitamin D, which are not always provided in clinical practice; in fact, we have seen patients stop taking their calcium and vitamin D supplements when they are started on prescription medication for osteoporosis. Moreover, patients in clinical trials are screened for secondary causes of osteoporosis and excluded if these are found. In practice, secondary causes of osteoporosis are common,21, 22 yet many patients go untested and untreated. A study of clinical practice patients showed that ∼10% of those treated with oral bisphosphonates had a significant loss of BMD over 1–2 yr, and many of the BMD-losers had a previously unrecognized contributing disease.23 Bell et al. extrapolate their analysis of FIT (which used 5 mg of daily alendronate for the first 2 yr—one half the usual prescribed dose) to make generalizations regarding all older women taking all currently clinically relevant doses and dosing intervals of alendronate and other orally administered bisphosphonates (risedronate or ibandronate). This extrapolation is probably not appropriate. Interestingly, some of these same authors made a similar extrapolation from perindopril to all angiotensin-enzyme converting inhibitors in their earlier article on blood pressure monitoring.11 It is instructive to look at the “best case” response to alendronate or risedronate in the Fosamax-Actonel Comparison Trial (FACT).24 The “responder” analysis looked at the percentage of these carefully screened and compliant women who had what would in clinical practice likely be called a significant decline in BMD. At 1 yr, 3% of women treated with alendronate and 7% of women treated with risedronate had a significant decline in BMD at the total hip, and, at the femoral neck, significant decreases were seen in 9% of those treated with alendronate and 14% of those treated with risedronate.25 Because not all patients who are prescribed medications for osteoporosis will maintain or have significant increases in BMD, monitoring with DXA can be used to identify patients who have significant decreases in BMD on therapy, decreases that can be the result of nonresponse to the medication, poor compliance, poor persistence, incorrect dosing, malabsorption or secondary causes of osteoporosis that were either unrecognized before starting treatment or developed after treatment was initiated. The dangers in extrapolating the results of the analysis of Bell et al. to clinical practice are further evident when examining patients treated with generic alendronate. A recent study has shown significant differences in the in vitro disintegration rates of generic alendronate from eight different manufacturers.26 Others have suggested lesser gains in BMD (40–50% lower) when generic alendronate was compared with branded alendronate and risedronate.27 Although within-subject variability is not an important part of their argument against serial BMD for monitoring treatment, that should still be addressed. Bell et al. stated there was “considerable within-person variation” that was statistically significant between patients in the treatment and in the placebo arms. The actual variance was 0.012 g/cm2 in the treated group and 0.014 g/cm2 in the placebo group. Although this difference may be statistically significant, it is not clinically relevant. With a mean BMD of ∼0.700 g/cm2, this “considerable” variation amounts to 1.7–2.0%, which is less than the variation seen in commonly used clinical measurements such as height, blood pressure, blood sugar, and cholesterol. Very few biological variables can be measured with the same precision as BMD. The International Society for Clinical Densitometry (ISCD) has established, updated, and promoted quality standards for BMD testing, including precision assessment to determine reproducibility. For serial BMD measurements, the ISCD has emphasized the concept of LSC to distinguish between random variation and true biological change.6, 25, 28 This important concept has not been embraced in other areas of clinical medicine that rely on quantitative measures for clinical decision-making. The application of precision and LSC to serial monitoring of BMD by expert densitometrists raises bone densitometry to a higher level than most quantitative measures in clinical medicine. It also means that the within-person variation cited by Bell et al. would not confound or confuse the interpretation of serial BMD measurements by those who appreciate the limitations. Strategies to improve poor adherence with pharmacologic treatment are desperately needed. Persistence was increased by a nurse visit29 and by positive reinforcement with bone turnover markers.30 Whether repeating BMD measurement after 1 or 2 yr of treatment might improve adherence is unknown; more study is needed to evaluate to what degree compliance and persistence are affected by repeating BMD after 1 or 2 yr. In the absence of such studies, it is premature to conclude that repeat densitometry is of no value. Currently, bone densitometry is the only technical examination to fill the clinical vacuum of follow-up in patients who embark on a long-term treatment regimen. In our opinion, the assumptions and conclusions of Bell et al., based on a post hoc analysis of FIT, are seriously flawed. Even with the most generous interpretation, their findings are only applicable to the unique population of subjects studied, treated with the 5-mg daily dose of alendronate used in FIT, and should not be generalized to the same drug taken in different doses or other drugs in the same class in the heterogeneous population of patients seen in clinical practice. Although it is unknown whether repeating BMD improves adherence with treatment, the true purpose of monitoring BMD in patients treated for osteoporosis is to identify the small but substantial number of patients who experience a significant decrease in BMD. These patients should be considered for further evaluation to search for the cause or causes of their decline in BMD, which may include poor compliance with the treatment program, deficient calcium/vitamin D intake, malabsorption, confounding diseases/disorders/medications with adverse skeletal effects, or true nonresponse to the drug. It is clear that BMD response rates in FIT are not representative of those seen in clinical practice. We suggest that until there is good evidence to do otherwise, clinicians should consider a follow-up BMD test ∼1 yr after starting pharmacologic therapy for osteoporosis and thereafter at intervals determined by individual patient circumstances.

Using national Medicare data from 1999–2006, we evaluated the relationship between travel distance and receipt of dual-energy X-ray absorptiometry (DXA). After adjusting for potentially confounding factors, travel distance was strongly associated with DXA testing. Rural residents were most strongly dependent on the availability of DXAs performed in physician offices.

Although the Bone Mass Measurement Act outlines the indications for central dual-energy X-ray absorptiometry (DXA) testing for US Medicare beneficiaries, the specifics regarding the appropriate ICD-9 codes to use for covered indications have not been specified by Medicare and are sometimes ambiguous. We describe the extent to which DXA reimbursement was denied by gender and age of beneficiary, ICD-9 code submitted, time since previous DXA, whether the scan was performed in the physician's office and local Medicare carrier. Using Medicare administrative claims data from 1999 to 2005, we studied a 5% national sample of beneficiaries age > or =65 yr with part A+B coverage who were not health maintenance organization enrollees. We identified central DXA claims and evaluated the relationship between the factors listed above and reimbursement for central DXA (CPT code 76075). Multivariable logistic regression was used to evaluate the independent relationship between DXA reimbursement, ICD-9 diagnosis code, and Medicare carrier. For persons who had no DXA in 1999 or 2000 and who had 1 in 2001 or 2002, the proportion of DXA claims denied was 5.3% for women and 9.1% for men. For repeat DXAs performed within 23 mo, the proportion denied was approximately 19% and did not differ by sex. Reimbursement varied by more than 6-fold according to the ICD-9 diagnosis code submitted. For repeat DXAs performed at <23 mo, the proportion of claims denied ranged from 2% to 43%, depending on Medicare carrier. Denial of Medicare reimbursement for DXA varies significantly by sex, time since previous DXA, ICD-9 diagnosis code submitted, place of service (office vs facility), and local Medicare carrier. Greater guidance and transparency in coding policies are needed to ensure that DXA as a covered service is reimbursed for Medicare beneficiaries with the appropriate indications.