National Bone Health Alliance Research Articles

A novel approach for assessing osteoporosis utilizing DXA, HU and VBQ

ObjectiveTo precisely assess preoperative osteoporosis in patients, a more precise method for evaluating osteoporosis is being developed to better guide the use of bone cement reinforced screws. MethodThe retrospective analysis was conducted on patients who underwent posterior lumbar decompression and fusion internal fixation at Shanghai Tongren Hospital.The general information, bone mineral density assessment data, Fracture risk prediction rate(WHO Fracture Risk Assessment Tool (FRAX)), and whether to use cement reinforced screws were collected. Definition of combination method: T value ​< ​−2.5 or HU value ​< ​110 or VBQ >3.5.The diagnostic rates of osteoporosis were compared between dual energy x-ray absorptiometry(DXA), Hounsfield Units(HU), Vertebral Bone Quality (VBQ), National Bone Health Alliance(NBHA), and combination methods, and the correlation between different methods was analyzed. Binary logistic regression was used to analyze the significant influencing factors of the use of cement-reinforced screws. ResultA total of 178 patients were enrolled in the study, aged 65.73 ​± ​14.43 years, 121 female, 57 male, Body Mass Index(BMI) was 22.88 ​± ​3.52, 57 (32.0%) used cement reinforced screws, and 14 (7.9%) had previous fracture history.The diagnostic rates of osteoporosis by DXA, HU, VBQ, NBHA and combination method were 22.5% (40/178), 47.2% (84/178), 56.2% (100/178), 64.0% (114/178) and 75.8% (135/178), respectively.HU, VBQ, NBHA, and combination methods were significantly different from DXA in the diagnosis rate of osteoporosis (P ​< ​0.001). Binary Logistics regression showed that age, T value, HU value, and VBQ value significantly influenced bone cement screw use, and the odds ratio of VBQ was 4.315. The prediction accuracy of the regression equation was 90.4%, the area under the receiver operator characteristic(ROC) curve was 0.974, and the Youden index was 0.830. ConclusionCurrently, the DXA method widely used for diagnosing osteoporosis yields false negative results and there are significant discrepancies among different diagnostic methods. The combined approach exhibits a higher detection rate (75.8%). Age, T value, HU value, and VBQ value significantly influence the use of cement screws with a regression equation accuracy of 90.4%. Cement-reinforced screws are recommended when osteoporosis is determined by a combination method.

09 Characteristics of Community Fallers and the Diagnosis of Osteoporosis in the Falls Clinic of a Public Tertiary Hospital

Abstract Introduction Osteoporosis is a chronic asymptomatic condition. The US National Bone Health Alliance recommends that osteoporosis may be diagnosed by bone mineral density (BMD) testing, the occurrence of low-trauma fractures or through the use of fracture risk algorithms. However, osteoporosis has low screening rates despite having clear treatment benefits. Methodology This study aimed to describe the characteristics of patients in the falls clinic with and without osteoporosis and the ways by which diagnosis of osteoporosis was made. A retrospective, descriptive study was carried out on all patients who attended the falls clinic from January 2015 till March 2019, with data collected from its falls database. Results A total of 117 patients were included in this study. All patients had a history of fall, either single or recurrent. 43 patients had osteoporosis, of which 72.1% were female (p value &amp;lt;0.05). In this study, age and ethnicity were not found to be risk factors for osteoporosis. Polypharmacy, having three or more comorbidities along with alcohol and smoking habits were also not significantly associated with osteoporosis. This study also showed no differences in terms of history of recurrent falls and level of mobility between the two groups of patients. Of the 43 patients with osteoporosis, six patients (14.0%) were diagnosed by BMD testing prior to their attendance at the falls clinic. 24 patients (55.8%) had a presumptive diagnosis of osteoporosis made based on prior fragility fracture, of which majority were vertebral fractures (45.8%); and the remaining 13 patients (32.0%) were diagnosed to have osteoporosis by BMD testing after their visit to the falls clinic. Conclusion Most patients who attended the falls clinic have had a prior fragility fracture, which could have been prevented by treatment. Screening for osteoporosis should therefore be carried out more robustly in the community to prevent injurious falls.

Association of Disease Definition, Comorbidity Burden, and Prognosis With Hip Fracture Probability Among Late-Life Women

Advanced age is associated with lower use of drug treatment to prevent fractures, but concerns about comorbidities and prognosis increase the complexity of managing osteoporosis in this age group. To determine the association of disease definition, number of comorbidities, and prognosis with 5-year hip fracture probabilities among women who are 80 years and older. This prospective cohort study (4 US sites) included 1528 community-dwelling women identified as potential candidates for initiation of osteoporosis drug treatment. Women were contacted every 4 months to ascertain vital status and hip fracture. Five-year hip fracture probability was calculated accounting for competing mortality risk. Participants were classified into 2 distinct groups based on disease definition criteria proposed by the National Bone Health Alliance: with osteoporosis (n = 761) and without osteoporosis but at high fracture risk (n = 767). Comorbid conditions were assessed by self-report. Prognosis was estimated using a mortality prediction index. All analysis was performed between March 2018 and January 2019. The study had 1528 participants, all of whom were women, with a mean (SD) age of 84.1 (3.4) years. During follow-up, 125 (8.0%) women experienced a hip fracture and 287 (18.8%) died before experiencing this event. Five-year mortality probability was 24.9% (95% CI, 21.8-28.1) among women with osteoporosis and 19.4% (95% CI, 16.6-22.3) among women without osteoporosis but at high fracture risk. In both groups, mortality probability similarly increased with more comorbidities and poorer prognosis. In contrast, 5-year hip fracture probability was 13.0% (95% CI, 10.7-15.5) among women with osteoporosis and 4.0% (95% CI, 2.8-5.6) among women without osteoporosis but at high fracture risk. The difference was most pronounced among women with more comorbidities or worse prognosis. For example, among women with 3 or more comorbid conditions, hip fracture probability was 18.1% (95% CI, 12.3-24.9) among women with osteoporosis vs 2.5% (95% CI, 1.3-4.2) among women without osteoporosis but at high fracture risk. Women 80 years and older who have osteoporosis, including those with more comorbidities or poorer prognosis, have a high 5-year probability of hip fracture despite accounting for competing mortality risk. In contrast, among women without osteoporosis but at high fracture risk, competing mortality risk far outweighs hip fracture probability, especially among those with more comorbidities or worse prognosis.

Use of CTX-I and PINP as bone turnover markers: National Bone Health Alliance recommendations to standardize sample handling and patient preparation to reduce pre-analytical variability

The International osteoporosis foundation and the International federation of clinical chemistry (IFCC) Bone marker standards working group have identified N-terminal propeptide of type I procollagen (PINP) and C-terminal telopeptide of type I collagen (CTX-I) in blood to be the reference markers of bone turnover for the fracture risk prediction and monitoring of osteoporosis treatment. Although used in clinical research for many years, bone turnover markers (BTM) have not been widely adopted in clinical practice primarily due to their poor within-subject and between-lab reproducibility. The NBHA bone turnover marker project team aim to reduce pre-analytical variability of CTX-I and PINP measurements through standardized sample handling and patient preparation. Recommendations for sample handling and patient preparations were made based on review of available publications and pragmatic considerations to reduce pre-analytical variability. Controllable and un-controllable patient-related factors were reviewed to facilitate interpretation and sample collection. Samples for CTX-I must be collected consistently in the morning hours in the fasted state. EDTA plasma is preferred for CTX-I for its greater sample stability. Sample collection conditions for PINP are less critical as PINP has minimal circadian variability and is not affected by food intake. Sample stability limits should be observed. The uncontrollable aspects (age, sex, pregnancy, immobility, recent fracture, co-morbidities, anti-osteoporotic drugs, other medications) should be considered in BTM interpretation. Adopting standardized sample handling and patient preparation procedures will significantly reduce controllable pre-analytical variability. The successful adoption of such recommendations necessitates the close collaboration of various stakeholders at the global stage, including the laboratories, the medical community, the reagent manufacturers and the regulatory agencies.

The epidemiology of osteoporosis in Italian postmenopausal women according to the National Bone Health Alliance (NBHA) diagnostic criteria: a multicenter cohort study.

The study was aimed at evaluating the prevalence of osteoporosis, defined by BMD and the National Bone Health Alliance (NBHA) criteria, and the prevalence of clinical risk factors for fractures in Italian postmenopausal women. This is a cross-sectional, multicenter, cohort study evaluating 3247 postmenopausal women aged ≥50 and older in different areas of Italy in the period 2012-2014. All the participants were evaluated as far as anthropometrics; questionnaires for FRAX® and DeFRA calculation were administered and bone mineral density was measured at lumbar spine, femoral neck and total hip by DXA. The prevalence of osteoporosis, as assessed by BMD and NBHA criteria was 36.6 and 57%, respectively. Mean±SD values of FRAX® and DeFRA were: 10.2±7.3 and 11±9.4 for major fractures, and 3.3±4.9 and 3.9±5.9 for hip fractures, respectively. Among clinical risk factors for fracture, the presence of previous fracture, particularly non-spine/non-hip fracture, parental history of hip fracture and current smoking were the most commonly observed. Our study showed that more that the half of postmenopausal women aged 50 and older in Italy has osteoporosis on the basis of the NBHA criteria. There is a relevant high risk of femur fracture, as assessed by the FRAX® and DeFRA and previous fracture, parental history of hip fracture and current smoking are the most common risk factors. The data should be considered particularly in relation to the need to increase prevention strategies on modifiable risk factors and therapeutic intervention.

The impact of the new National Bone Health Alliance (NBHA) diagnostic criteria on the prevalence of osteoporosis in the United States: supplementary presentation.

We evaluated the prevalence of osteoporosis using the osteoporosis diagnostic criteria developed by the National Bone Health Alliance (NBHA), which includes qualified fractures, FRAX score in addition to BMD. The expanded definition increases the prevalence compared to BMD alone definitions; however, it may better identify those at elevated fracture risk. Recently an NBHA working Group published a paper in OI with recommendations for expanding the criteria that would constitute an osteoporosis diagnosis in postmenopausal women and in men over age 50 for use in the US - Siris et al., Osteoporosis International 25(%): 1439-1443, 2014. The recommendations have now been endorsed by NOF, ASBMR and a number of professional medical groups and appear in the NOF Clinician's Guide. The new diagnostic criteria continue to include a T-score by DXA of spine or hip that is less than or equal to -2.5, but alternatively also include a hip fracture with or without BMD testing or a vertebral, pelvis, proximal humerus and in some cases a distal forearm fracture in a person with low bone mass, or a FRAX score that meets or exceeds the NOF Guide osteoporosis treatment cut point.

Use of CTX-I and PINP as bone turnover markers: National Bone Health Alliance recommendations to standardize sample handling and patient preparation to reduce pre-analytical variability.

The IOF and the International Federation of Clinical Chemistry (IFCC) Bone Marker Standards Working Group have identified PINP and CTX-I in blood to be the reference markers of bone turnover for the fracture risk prediction and monitoring of osteoporosis treatment. Although used in clinical research for many years, bone turnover markers (BTM) have not been widely adopted in clinical practice primarily due to their poor within-subject and between-lab reproducibility. The NBHA Bone Turnover Marker Project team aim to reduce pre-analytical variability of CTX-I and PINP measurements through standardized sample handling and patient preparation. Recommendations for sample handling and patient preparations were made based on review of available publications and pragmatic considerations to reduce pre-analytical variability. Controllable and un-controllable patient-related factors were reviewed to facilitate interpretation and sample collection. Samples for CTX-I must be collected consistently in the morning hours in the fasted state. EDTA plasma is preferred for CTX-I for its greater sample stability. Sample collection conditions for PINP are less critical as PINP has minimal circadian variability and is not affected by food intake. Sample stability limits should be observed. The uncontrollable aspects (age, sex, pregnancy, immobility, recent fracture, co-morbidities, anti-osteoporotic drugs, other medications) should be considered in BTM interpretation. Adopting standardized sample handling and patient preparation procedures will significantly reduce controllable pre-analytical variability. The successful adoption of such recommendations necessitates the close collaboration of various stakeholders at the global stage, including the laboratories, the medical community, the reagent manufacturers and the regulatory agencies.

The impact of the new National Bone Health Alliance (NBHA) diagnostic criteria on the prevalence of osteoporosis in the USA.

The purpose of this paper is to estimate the prevalence of osteoporosis in US adults ≥50years using the NBHA osteoporosis diagnostic criteria. Utilizing 2005-2008 data of the National Health and Nutrition Examination Survey (NHANES), we identified participants with osteoporosis with any one of the following: (1) femoral neck or lumbar spine T-score≤-2.5; (2) low trauma hip fracture irrespective of BMD or clinical vertebral, proximal humerus, pelvis, or distal forearm fracture with a T-score >-2.5 <-1.0; or (3) FRAX score at the National Osteoporosis Foundation intervention thresholds (≥3% for hip fracture or ≥20% for major osteoporotic fracture). We estimated the prevalence overall and by gender and age. Our sample included 1948 (54.3%) men and 1639 (45.7%) women. Approximately 12% were 80+ years and 21% were from racial/ethnic minority groups. We estimated that 16.0% (0.8) of men and 29.9% (1.0) of women 50+ years have osteoporosis. The prevalence increases with age to 46.3% in men and 77.1% in women 80+ years. The combination of FRAX score and fractures was the largest contributing factor defining osteoporosis in men (70-79, 88.1%; 80+, 80.1%), whereas T-score was the largest contributing factor in women (70-79, 49.2%; 80+, 43.5%). We found that 16% of men and 29.9% of women 50+ have osteoporosis based on the NBHA diagnostic criteria. Although the expanded definition increases the prevalence compared to BMD alone-based definitions, it may better identify those at elevated fracture risk in order to reduce the burden of fractures in older adults.

Predicting fracture risk in osteoporosis: the use of fracture prediction tools in an osteoporosis clinic population

BackgroundIn the UK, the National Institute for Health and Care Excellence recommends either fracture risk assessment tool (FRAX) or QFracture to estimate the 10 year fracture risk of individuals. However,...

The Osteoporosis Clinical Care Gap: An Opportunity for Impact by the Clinical Pharmacist

The impact of osteoporosis to patients and the healthcare system is significant with estimates that 50% of Caucasian women and 20% of men will experience an osteoporotic fracture in their lifetime. However, despite multiple calls to action from healthcare advocates, osteoporosis remains underdiagnosed and undertreated. Data demonstrates that only 23% of women aged 67 years old and older who have an osteoporosis-related fracture receive either a bone mineral density test or a prescription to treat osteoporosis in the six months after the fracture. Reasons for this are debatable but may be include lack of access to DXA, an over reliance on T-scores, and a lack of recognition on the importance of the evaluation of clinical risk factors. In 2014 the National Bone Health Alliance released a position statement regarding the diagnosis of osteoporosis which suggested new standards for the diagnosis of osteoporosis. Through utilization of these new standards, pharmacists are one of the healthcare providers in an interdisciplinary team which may help to recognize osteoporosis diagnoses and the need for treatment, closing the care gap that currently exists with osteoporosis.

Betsy McClung 1942-2015.

Betsy McClung The osteoporosis world and the world in general has lost one of its finest women. Betsy McClung died peacefully on the morning of September 10, 2015, with her husband, Mike, and her daughter, Holly, at her home bedside after a long and courageous battle with pancreatic cancer. Our hearts and deep feelings go out to Mike McClung and all of Betsy's family. She will be missed and remembered. She will be remembered not only because of her ever-present smile and positive outlook on life but also because of her commitment to the broad field of osteoporosis. As a dear friend of Mike and Betsy, let me impart some of her key accomplishments in life, notwithstanding her greatest accomplishment: a committed wife, mother, and companion. Betsy was a pioneer in educating nurses about osteoporosis management, and in this capacity she founded the ASBMR Annual Meeting session on Allied Health in 1996, a session that will be continued in her memory this year in Seattle by Professors John Bilezikian and Roland Baron. Betsy was a board member of the North American Menopause Society and the Paget's Foundation, leading by example, by patience, and by gentle persuasive persistence. She and Mike cofounded the Oregon Osteoporosis Center (OOC) in 1986 and in that capacity made the OOC one of the world's foremost recognized and respected osteoporosis diagnostic and treatment facilities and a leading center in international clinical trials. Betsy was educated (both bachelor and master of science in nursing) at the University of Oregon, and from that point developed an unwavering passion for caring for patients with osteoporosis. In time, she became an icon in the education of nurses and other allied health professionals. This impact will be her memorial in our metabolic bone field. In 1987 she and Mike met, and a unique and loving relationship evolved that went beyond marriage and business, a real dual partnership. They shared three children: Holly Love, now also a registered nurse; Andy Love; and Daniel McClung. Betsy made sure that they were all successfully integrated with a true sense of family. My wife, Linda, and I were a part of the privacy of their new and bonding relationship from the beginning, and the stories we have collected together and the places we have visited over 40 years will be forever a part of us. We are grateful. Betsy and Mike developed bonds that created lifelong friendships on an international scale and, by these trusted bonds, influenced the osteoporosis world in ways that we all recognize and that will leave a lasting legacy. A few among many respected pioneers in the field can be counted as a reflection of the enormous influence Betsy and Mike imparted in our bone field: Professors John Kanis, Harry Genant, Claus Christiansen, Graham Russell, Herbie Fleisch, Socrates Papapoulos, Nelson Watts, John Bilezikian, Larry Raisz, Lou Avioli, Larry Riggs, Ego Seeman, Pierre Delmas, and Juliet Compston, just to name a few. Betsy was a woman unabashedly generous with love and support in a world that now needs her presence and her principles more than ever. There was not an ounce of negativity in her soul. The American Society for Bone and Mineral Research, the International Osteoporosis Foundation, the North American Menopausal Society, the National Osteoporosis Foundation, and the National Bone Health Alliance all had their missions influenced in a creative manner one way or another by Betsy's touch. The absence of that touch will be felt by all, but her impact on us will never be forgotten. Paul D Miller Distinguished Clinical Professor of Medicine University of Colorado Health Sciences Center Medical Director Colorado Center for Bone Research Lakewood, Colorado 80227

Intervention Thresholds and the Diagnosis of Osteoporosis.

A position paper of the National Bone Health Alliance recently recommended that diagnostic criteria for osteoporosis be redefined. We review the merits and demerits of this proposal and argue that the operational bone mineral density (BMD)-based definition be retained while clarity is brought to bear on the distinction between diagnostic and intervention thresholds.

National Bone Health Alliance: A Multi-Sector Public-Private Partnership Working Together to Improve America's Bone Health

There have been many scientific advances in fracture risk prediction beyond bone density. The International Society for Clinical Densitometry (ISCD) convened a Position Development Conference (PDC) on the use of dual-energy X-ray absorptiometry beyond measurement of bone mineral density for fracture risk assessment, including trabecular bone score and hip geometry measures. Previously, no guidelines for nonbone mineral density DXA measures existed. Furthermore, there have been advances in the analysis of quantitative computed tomography (QCT) including finite element analysis, QCT of the hip, DXA-equivalent hip measurements, and opportunistic screening that were not included in the previous ISCD positions. The topics and questions for consideration were developed by the ISCD Board of Directors and the Scientific Advisory Committee and were designed to address the needs of clinical practitioners. Three task forces were created and asked to conduct comprehensive literature reviews to address specific questions. The task forces included participants from many countries and a variety of interests including academic institutions and private health care delivery organizations. Representatives from industry participated as consultants to the task forces. Task force reports with proposed position statements were then presented to an international panel of experts with backgrounds in bone densitometry. The PDC was held in Chicago, Illinois, USA, contemporaneously with the Annual Meeting of the ISCD, February 26 through February 28, 2015. This Executive Summary describes the methodology of the 2015 PDC on advanced measures from DXA and QCT and summarizes the approved official positions. Six separate articles in this issue will detail the rationale, discussion, and additional research topics for each question the task forces addressed.

Diagnostic criteria for osteoporosis should be expanded

As a relatively newly classified chronic disease, scientific enquiry about pathophysiology, diagnosis, and treatment for osteoporosis has rapidly increased in the past three decades. Under the direction of the National Bone Health Alliance, a working group has proposed expansion of the diagnostic criteria for osteoporosis in men and postmenopausal women aged 50 years and older to include individuals with any of the following: a hip fracture (with or without bone mineral density [BMD] testing); low bone mass as determined by BMD and a vertebral, proximal humeral, pelvic, or, in some cases, distal forearm fracture; or raised fracture risk based on the WHO fracture risk algorithm, FRAX.

Mechanistic and therapeutic insights into skeletal biology learned from the study of rare bone diseases

To date, nearly 500 unique rare bone diseases have been described,which in the aggregate affect 1 in 5000 live births and comprise 5% of all birth defects. Currently, the overwhelming majority of these disorders have no cure. Studying rare bone diseases has helped elucidate biological pathways and reveal valuable therapeutic targets that also benefit patients with common bone diseases. In an effort to engage scientists, clinicians, young investigators, advocacy groups and representatives of the pharmaceutical industry in fruitful discussion of how the study and treatment of rare bone diseases has helped, and will continue to help, expand our understanding of bone health, The National Bone Health Alliance and Rare Bone Disease Patient Network sponsored this workshop in partnership with the American Society for Bone and Mineral Research and the United States Bone and Joint Initiative.

The clinical diagnosis of osteoporosis: a position statement from the National Bone Health Alliance Working Group

SummaryOsteoporosis causes an elevated fracture risk. We propose the continued use of T-scores as one means for diagnosis but recommend that, alternatively, hip fracture; osteopenia-associated vertebral, proximal humerus, pelvis, or some wrist fractures; or FRAX scores with ≥3 % (hip) or 20 % (major) 10-year fracture risk also confer an osteoporosis diagnosis.IntroductionOsteoporosis is a common disorder of reduced bone strength that predisposes to an increased risk for fractures in older individuals. In the USA, the standard criterion for the diagnosis of osteoporosis in postmenopausal women and older men is a T-score of ≤ −2.5 at the lumbar spine, femur neck, or total hip by bone mineral density testing.MethodsUnder the direction of the National Bone Health Alliance, 17 clinicians and clinical scientists were appointed to a working group charged to determine the appropriate expansion of the criteria by which osteoporosis can be diagnosed.ResultsThe group recommends that postmenopausal women and men aged 50 years should be diagnosed with osteoporosis if they have a demonstrable elevated risk for future fractures. This includes having a T-score of less than or equal to −2.5 at the spine or hip as one method for diagnosis but also permits a diagnosis for individuals in this population who have experienced a hip fracture with or without bone mineral density (BMD) testing and for those who have osteopenia by BMD who sustain a vertebral, proximal humeral, pelvic, or, in some cases, distal forearm fracture. Finally, the term osteoporosis should be used to diagnose individuals with an elevated fracture risk based on the World Health Organization Fracture Risk Algorithm, FRAX.ConclusionsAs new ICD-10 codes become available, it is our hope that this new understanding of what osteoporosis represents will allow for an appropriate diagnosis when older individuals are recognized as being at an elevated risk for fracture.

Systematic approaches to fragility fracture prevention

SummaryIndividuals who have suffered fractures caused by osteoporosis – also known as fragility fractures – are the most readily identifiable group at high risk of suffering future fractures. Globally, the majority of these individuals do not receive the secondary preventive care that they need. The Fracture Liaison Service model (FLS) has been developed to ensure that fragility fracture patients are reliably identified, investigated for future fracture and falls risk, and initiated on treatment in accordance with national clinical guidelines. FLS have been successfully established in Asia, Europe, Latin America, North America and Oceania, and their widespread implementation is endorsed by leading national and international osteoporosis organisations. Multi-sector coalitions have expedited inclusion of FLS into national policy and reimbursement mechanisms. The largest national coalition, the National Bone Health Alliance (NBHA) in the United States, provides an exemplar of achieving participation and consensus across sectors. Initiatives developed by NBHA could serve to inform activities of new and emerging coalitions in other countries.

National Bone Health Alliance: An Innovative Public-Private Partnership Improving America’s Bone Health

The U.S. National Bone Health Alliance (NBHA) is a public-private partnership launched in 2010 that brings together its 56 partners from the government, nonprofit, and for-profit sectors to collectively promote bone health and prevent disease; improve bone disease diagnosis and treatment; and enhance bone research, surveillance, and evaluation. NBHA is driven to achieve its 20/20 vision to reduce fractures 20% by the year 2020 through projects including 2Million2Many, an osteoporosis awareness campaign; Fracture Prevention CENTRAL, an online resource center providing support to sites interested in launching a secondary fracture prevention program; bone turnover marker standardization project; and working groups in rare bone disease and the clinical diagnosis of osteoporosis. NBHA provides a platform to coordinate messaging among individuals and organizations on subjects important to bone health; pool funding and efforts around shared priorities; and work together towards the goals and recommendations of the National Action Plan on Bone Health.

Harmonization in laboratory medicine: the complete picture

Evidence of the acute lack of interchangeable laboratory results and consensus in current practice among clinical laboratories has underpinned greater attention to standardization and harmonization projects. Although the focus is mainly on the standardization of measurement procedures, the scope of harmonization goes beyond method and analytical results: it includes all other aspects of laboratory testing, including terminology and units, report formats, reference intervals and decision limits, as well as test profiles and criteria for the interpretation of results. This review provides further insight on the issue of harmonization in laboratory medicine in view of the urgent need for a complete picture now that old and new drivers are calling for more effective efforts in this field. The main drivers for standardization and harmonization projects are first and foremost patient safety, but also the increasing trends towards consolidation and networking of clinical laboratories, accreditation programs, clinical governance, and advances in Information Technology (IT), including the electronic patient record. The harmonization process, which should be considered a three-tier approach involving local, national and international fronts, must go beyond the harmonization of methods and analytical results to include all other aspects of laboratory testing. A pertinent example of the importance of a complete picture in harmonization programs is given by the National Bone Health Alliance working in the field of bone turnover markers in cooperation with scientific societies including the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC).

National Bone Health Alliance Bone Turnover Marker Project: current practices and the need for US harmonization, standardization, and common reference ranges.

This position paper reviews how the National Bone Health Alliance (NBHA) will execute a project to help assure health professionals of the clinical utility of bone turnover markers; the current clinical approaches concerning osteoporosis and the status and use of bone turnover markers in the USA; the rationale for focusing this effort around two specific bone turnover markers; the need to standardize bone marker sample collection procedures, reference ranges, and bone turnover marker assays in clinical laboratories; and the importance of harmonization for future research of bone turnover markers. Osteoporosis is a major global health problem, with the prevalence and incidence of osteoporosis for at-risk populations estimated to be 44 million Americans. The potential of bone markers as an additional tool for health care professionals to improve patient outcomes and impact morbidity and mortality is crucial in providing better health care and addressing rising health care costs. This need to advance the field of bone turnover markers has been recognized by a number of organizations, including the International Osteoporosis Foundation (IOF), National Osteoporosis Foundation, International Federation of Clinical Chemistry, and Laboratory Medicine (IFCC), and the NBHA. This position paper elucidates how this project will standardize bone turnover marker sample collection procedures in the USA, establish a USA reference range for one bone formation (serum procollagen type I N propeptide, s-PINP) and one bone resorption (serum C-terminal telopeptide of type I collagen, s-CTX) marker, and standardize bone turnover marker assays used in clinical laboratories. This effort will allow clinicians from the USA to have confidence in their use of bone turnover markers to help monitor osteoporosis treatment and assess future fracture risk. This project builds on the recommendations of the IOF/IFCC Bone Marker Standards Working Group by developing USA reference standards for s-PINP and s-CTX, the markers identified as most promising for use as reference markers. The goals of this project will be realized through the NBHA and will include its governmental, academic, for-profit, and non-profit sector stakeholders as well as major academic and commercial laboratories. Upon completion, a parallel effort will be pursued to make bone turnover marker measurements reliable and accepted by all health care professionals for facilitating treatment decisions and ultimately be reimbursed by all health insurance payers. Successful completion of this project will help assure health professionals from the USA of the clinical utility of bone turnover markers and ties in with the parallel effort of the IOF/IFCC to develop worldwide bone turnover reference ranges.