Current Osteoporosis Management Research Articles

Up-to-Date Knowledge on Osteoporosis Treatment Selection in Postmenopausal Women.

The concept of a super-aged society has led to a steady increase in the average lifespan and hence, interest in a healthy life has increased. Aging is a major risk factor for many diseases, including osteoporosis. Osteoporotic fractures have a significant impact on the quality of life of the elderly and hence, it is pivotal to provide effective treatment of osteoporosis after menopause. Osteoporosis requires proper management and the treatment must be centered on long-term goals. New drugs with diverse mechanisms have been developed for treating osteoporosis. Current management of osteoporosis generally focuses on the importance of risk-based strategies to maximize the effectiveness of existing treatments and mitigate potential negative side-effects. Additionally, there is a need for sequential treatment of osteoporosis in the future. This review discusses the dynamic strategies for osteoporosis treatment and the importance of long-term management in postmenopausal women.

Secondary Osteoporosis.

Osteoporosis is a global public health problem, with fractures contributing to significant morbidity and mortality. Although postmenopausal osteoporosis is most common, up to 30% of postmenopausal women, > 50% of premenopausal women, and between 50% and 80% of men have secondary osteoporosis. Exclusion of secondary causes is important, as treatment of such patients often commences by treating the underlying condition. These are varied but often neglected, ranging from endocrine to chronic inflammatory and genetic conditions. General screening is recommended for all patients with osteoporosis, with advanced investigations reserved for premenopausal women and men aged < 50 years, for older patients in whom classical risk factors for osteoporosis are absent, and for all patients with the lowest bone mass (Z-score ≤ -2). The response of secondary osteoporosis to conventional anti-osteoporosis therapy may be inadequate if the underlying condition is unrecognized and untreated. Bone densitometry, using dual-energy x-ray absorptiometry, may underestimate fracture risk in some chronic diseases, including glucocorticoid-induced osteoporosis, type 2 diabetes, and obesity, and may overestimate fracture risk in others (eg, Turner syndrome). FRAX and trabecular bone score may provide additional information regarding fracture risk in secondary osteoporosis, but their use is limited to adults aged ≥ 40 years and ≥ 50 years, respectively. In addition, FRAX requires adjustment in some chronic conditions, such as glucocorticoid use, type 2 diabetes, and HIV. In most conditions, evidence for antiresorptive or anabolic therapy is limited to increases in bone mass. Current osteoporosis management guidelines also neglect secondary osteoporosis and these existing evidence gaps are discussed.

Romosozumab in the treatment of osteoporosis.

Osteoporosis is a disease characterized by weakening of the bone architecture, which leads to an increased risk of fracture. There has been interest in the development of osteoanabolic agents that can increase bone mass and reverse the deteriorating architecture of osteoporotic bone. Romosozumab is a new agent for osteoporosis that both promotes bone formation and inhibits bone resorption. It is a monoclonal antibody that inhibits the activity of sclerostin, which allows the Wnt pathway to promote osteoblastogenesis and inhibit the activity of bone-resorbing osteoclasts. In clinical trials, it has proven to be superior to other agents in terms of increasing bone mineral density and reducing the incidence of fractures. This review will highlight the pharmacology, clinical efficacy and safety profile of romosozumab and suggest where this medication may fit within our current management of osteoporosis.

The impact of translational studies in the current management of osteoporosis

Recent technological and scientific advancements have changed the way through which knowledge is acquired through research. Until the early 1980s, research that was not hypothesis-oriented was considered an “anathema” within the scientific world. With the advent of high throughput methodologies in the early 1990s, a new approach to scientific research was created, namely “discovery-driven” research. These “opposite” approaches produced another discipline, named “translational research” (TR). In this sense, the investigation of diseases, such as osteoporosis, changed drastically. Osteoporosis is characterized by decreased bone mass and a deterioration of bone microarchitecture, leading to enhanced fragility and a subsequent increase in fracture risk. Osteoporosis is also known with the term “silent disease”, since it is often undetected until a low-energy fragility fracture occurs, which triggers further diagnosis and therapy. High throughput methodologies, combined with in vitro and in vivo studies have the potential to lead us to new prognostic and therapeutic targets of osteoporosis management. In the present work we review some of the important concepts of TR in the treatment and the future of osteoporosis. We have emphasized on the description of genomics and the use of in vitro and in vivo systems towards the understanding of osteoporosis pathogenesis and treatment.

Cost-effectiveness of pulse-echo ultrasonometry in osteoporosis management.

PurposeOsteoporosis is asymptomatic morbidity of the elderly which develops slowly over several years. Osteoporosis diagnosis has typically involved Fracture Risk Assessment (FRAX) followed by dual energy X-ray absorptiometry (DXA) in specialist care. Point-of-care pulse-echo ultrasound (PEUS) was developed to overcome DXA-related access issues and to enable faster fracture prevention treatment (FPT) initiation. The objective of this study was to evaluate the cost-effectiveness of two proposed osteoporosis management (POMs: FRAX→PEUS-if-needed→DXA-if-needed→FPT-if-needed) pathways including PEUS compared with the current osteoporosis management (FRAX→DXA-if-needed→FPT-if-needed).Materials and methodsEvent-based probabilistic cost–utility model with 10-year duration for osteoporosis management was developed. The model consists of a decision tree for the screening, testing, and diagnosis phase and is followed by a Markov model for the estimation of incidence of four fracture types and mortality. Five clinically relevant patient cohorts (potential primary FPT in women aged 75 or 85 years, secondary FPT in women aged 65, 75, or 85 years) were modeled in the Finnish setting. Generic alendronate FPT was used for those diagnosed with osteoporosis, including persistence overtime. Discounted (3%/year) incremental cost-effectiveness ratio was the primary outcome. Discounted quality-adjusted life-years (QALYs), payer costs (year 2016 value) at per patient and population level, and cost-effectiveness acceptability frontiers were modeled as secondary outcomes.ResultsPOMs were cost-effective in all patient subgroups with noteworthy mean per patient cost savings of €121/76 (ranges €107–132/52–96) depending on the scope of PEUS result interpretation (test and diagnose/test only, respectively) and negligible differences in QALYs gained in comparison with current osteoporosis management. In the cost-effectiveness acceptability frontiers, POMs had 95%–100% probability of cost-effectiveness with willingness to pay €24,406/QALY gained. The results were robust in sensitivity analyses. Even when assuming a high cost of PEUS (up to €110/test), POMs were cost-effective in all cohorts.ConclusionThe inclusion of PEUS to osteoporosis management pathway was cost-effective.

A health economic simulation model for the clinical management of osteoporosis.

The purpose of this study is to estimate the burden of osteoporosis in Sweden based on current clinical practice and the cost-effectiveness of improvements in the management of osteoporosis over the clinical management compared to current clinical practice. The analysis was carried out using a model that simulates the individual patients considered for pharmacological treatment during 1year and their projected osteoporosis treatment pathway, quality-adjusted life years (QALYs) and costs over their remaining lifetime. All patients regardless of treatment or no treatment were simulated. Information on current management of osteoporosis in terms of patient characteristics and treatment patterns were derived from a Swedish osteoporosis research database based on national registers and patient records. Current (standard) clinical management was compared with alternative scenarios mirroring Swedish treatment guidelines. The national burden in terms of lost QALYs was estimated at 14,993 QALYs and the total economic cost at €776M. Scenario analyses showed that 382-3864 QALYs could be gained at a cost/QALY ranging from cost-saving to €31368, depending on the scenario. The margin of investment, i.e. the maximum amount that could be invested in the healthcare system to achieve these improvements up to the limit of the willingness to pay/QALY, was estimated at €199M on a population level (€3,634/patient). The analysis showed that better compliance to treatment guidelines is associated with better projected outcomes and cost-savings. From a cost-effectiveness perspective, there is also considerable room for investment to achieve these improvements in the management of osteoporosis.

Screening for osteoporosis in Chinese post-menopausal women: a health economic modelling study.

Screening and appropriate treatment for osteoporosis has been proven to be cost-effective in many populations; however, it is not clear in the Chinese population. Simulations using a validated health economics model suggest that screening for osteoporosis in Chinese women is cost-effective and may even be cost-saving in Chinese post-menopausal women. This study aimed at determining the cost-effectiveness of osteoporosis screening strategies in post-menopausal Chinese women. A validated state-transition microsimulation model with a lifetime horizon was used to evaluate the cost-effectiveness of different screening strategies with treatment of alendronate compared with current osteoporosis management in China. Osteoporosis screening strategies assessed were (1) universal screening with dual-energy X-ray absorptiometry (DXA) alone; (2) Osteoporosis Self-Assessment Tool for Asians (OSTA) + DXA; and (3) quantitative ultrasound (QUS) + DXA with rescreening at 2, 5 or 10-year intervals for patients screened negative by DXA. The study was performed from the Chinese healthcare payer's perspective. All model inputs were retrieved from publically available literature. Uncertainties were addressed by one-way and probabilistic sensitivity analysis. Screening strategies all improved clinical outcomes at increased costs, and each were cost-effective compared with no screening in women aged 55years given the Chinese willingness-to-pay threshold of USD 20,000 per quality-adjusted life year (QALY) gained. Pre-screening with QUS and subsequent DXA screening if the QUS T-score ≤ -0.5 with a 2-year rescreening interval was the most cost-effective strategy with the highest probability of being cost-effective across all non-dominated strategies. Screening strategies were cost-saving if screenings were initiated from age 65years. One-way sensitivity analyses indicated that the results were robust. Pre-screening with QUS with subsequent DXA screening if the QUS T-score ≤ -0.5 with a 2-year rescreening interval in the Chinese women starting at age 55 is the most cost-effective. In addition, screening and treatment strategies are cost-saving if the screening initiation age is greater than 65years.

Use of Osteoporosis Medications after Hospitalization for Hip Fracture: A Cross-national Study

BackgroundAlthough current osteoporosis management guidelines recommend use of pharmacologic treatment after hip fracture, the care of such patients has been suboptimal. The objective of this cross-national study was to quantify the use of and adherence to osteoporosis medication after hip fracture in 3 countries with different healthcare systems—the United States, Korea, and Spain. MethodsIn 3 cohorts of patients aged ≥65 years hospitalized for hip fracture, we calculated the proportion receiving ≥1 osteoporosis drug after discharge. Adherence to osteoporosis treatment was measured as the proportion of days covered (PDC) during the first year after the hip fracture. ResultsWe identified 86,202 patients with a hip fracture: 4704 (US Medicare), 6700 (US commercial), 57,631 (Korea), and 17,167 (Spain). The mean age was 77-83 years, and 74%-78% were women. In the year before the index hip fracture, 16%-18% were taking an osteoporosis medication. Within 3 months after the index hip fracture, 11% (US Medicare), 13% (US commercial), 39% (Korea), and 25% (Spain) of patients filled ≥1 prescription for osteoporosis medication. For those who filled ≥1 prescriptions for an osteoporosis medication, the mean PDC in the year after the fracture was 0.70 (US Medicare), 0.67 (US commercial), 0.43 (Korea), and 0.66 (Spain). ConclusionsRegardless of differences in healthcare delivery systems and medication reimbursement plans, the use of osteoporosis medications for the secondary prevention of osteoporotic fracture was low. Adherence to osteoporosis treatment was also suboptimal, with the PDC <0.70 in all 3 countries.

日本総合健診医学会 第42回大会・教育講演8&lt;br&gt;骨検診の今後に期待されるもの

わが国は世界一の超高齢社会を構成しており、65歳以上の高齢者が年々増えている。このことは必然的に運動器疾患の1つである骨粗鬆症患者の増加をもたらし、脆弱性骨折は増加の一途を辿っている。骨粗鬆症の治療目的は骨折予防にあり、骨折リスクの高い患者は積極的に医療機関を受診してもらう必要がある。スターターとして、この受診勧奨の役割を果たしているのが人間ドックであり、骨検診である。 しかし、わが国の人間ドックや検診施設の70％が超音波（QUS）を用いている。このQUSは簡便でX線被爆もなく安全であるが、使用する機種によりパラメーターが異なり、データに普遍性がない。このためQUSは確定診断に用いることができず、スクリーニングとして共通の指標で基準値を示すことができないので、スクリーニングへの使用も疑問視されている。 そこでわが国で開発され、30年の歴史あるMD法を使用することを提案したい。このMD法はスクリーニングはもとより、直近の診断基準でも診断が可能な測定法であると認知されている。本法は短時間に多数例を測定でき、X線撮影装置さえあれば、特別な装置は必要としない。最近の改良型では従来の半分の線量になるなど、非侵襲性と即時報告が可能などの簡便性がある。さらにこの骨検診に運動機能を評価し得る「ロコチェック」を併用していただきたい。 一方最近、ビタミンDの指標である25（OH）Dの欠乏や不足が問題となっており、低骨密度や転倒リスク、さらには高い骨折リスク要因となっている。現時点では保険適応はないが、低骨密度で骨折リスクの高い患者群の検出に適したマーカーであるので、骨検診に加えることを推奨したい。 骨検診の意義は潜在患者を見つけ出し、治療へ導くことにあるので、加療に結びつく適切な検診というスタートがあってのゴールである。骨粗鬆症診療の現状を踏まえ、今後の骨検診のあり方を提案させていただいた。

Management of Osteoporosis: Who to Treat, What to Use, and for How Long?

Osteoporosis is a huge global problem both socially and economically- in the South Korea alone, in 2011 66 million dollar was spent on treatment and social care of the 773,000 osteoporotic patients- and therefore variable preventative and therapeutic approaches are keys to managing this problem within the aging population of today. This review discusses the main issues- who should be treated, what pharmacological agents should be used, and how long they should be administered- surrounding current osteoporosis management. Identifying patients at risk is challenging before they develop a fracture. Probability of fracture based on the Korea-adapted WHO algorithm should be used in making decision of treatment. Though bisphosphonates are the most commonly used drugs for the treatment of osteoporosis, the majority of data on fracture effect is from studies of 3 or 4 years. The long-term treatment should balance fracture efficacy against the risk of adverse events. Although evidence is limited regarding the risk of fracture with the continuation of bisphosphonate therapy, it might be useful to continue treat osteoporosis up to 10 years, to prevent vertebral fractures in the high risk elderly. There are currently no data to guide clinicians in determining who should continue treatment after 5 years. The duration of treatment and the agent selected should be based on individual assessment of risks and benefits and on patient preference. (Korean J Med 2013;85:364-373)

XXV Triennial World Congress – SICOT 2011

The Triennial World Congress in Prague in parallel with the exceptional evolution of our journal International Orthopaedics provides a very good image of the current expansion of SICOT by the quality of the scientific presentations and by the international representation in the different fields of orthopaedic surgery and traumatology. It reflects all the advantages of a global orthopaedic society. From 6 to 9 September 2011, you will be able to select your menu “a la carte” from 12 parallel sessions handled by the most renowned specialists in the world. The Congress will include five plenary conferences, 239 invited speakers, 11 symposia and 83 sessions devoted to free oral presentations to allow the active participation of a maximum number of participants. This year we inaugurate e-posters augmented by specific short oral presentations of a selection of them during focus poster sessions. As education represents a significant part of the objectives of SICOT, 18 instructional courses on the main topics and one educational day on the hip are scheduled. Instructional courses set out to cover exhaustively specific topics mostly aimed at young colleagues, and some will include hands-on demonstrations. The main subjects are: TKR balancing, revision of total knee arthroplasty, guided TKA: is it worth it?, lengthening of long bones, surgical management of spinal deformities, damage control in poly-traumatised patients, reverse shoulder arthroplasty, management of rotator cuff pathology, musculoskeletal tumours in children, distal radial fractures including a hands-on course, natural disasters and mass casualties, DVT prevention in orthopaedics and current management of osteoporosis. More specialised symposia give the present state of the art in other specific fields. This year, they will focus on high tibial osteotomy, cartilage repair, hip arthroscopy, modular stem prostheses of the hip, TB spine, ultrasound in orthopaedics and how to write and publish a paper, presented by the Editors of the main orthopaedic journals including International Orthopaedics. Trauma will be an important part of the meeting. The SICOT Trauma Committee, chaired by Vilmos Vecsei, will focus on fractures around the knee with one symposium and three free paper sessions on the subject. Controversial topics are also covered. To keep pace with the current tragic events in the world, a symposium on natural disasters will attempt to help the humanitarian volunteers in their assessment of the indications for amputation which always remains a difficult decision for the surgeon. The spine has received special attention with the support of our SICOT President Cody Bunger together with an open session of the Scoliosis Research Society. The different disciplines are highlighted by ten specialty societies’ sessions and symposia including the International Hip Society, Association for the Rational Treatment of Fractures (ARTOF), Computer Assisted Orthopaedic Surgery (CAOS), International Society for Minimal Intervention in Spine Surgery (ISMISS), European Society of Sport Traumatology, Knee Surgery and Arthroscopy and many others. Paediatric orthopaedics will be represented, as is now a tradition, by the International Federation of Paediatric Orthopaedic Societies (IFPOS) and the International Club Foot study group. A symposium on paediatric trauma and an instructional course on the Ponseti management of the club foot will complete the information. The industry is extensively represented with a large technical exhibition and special courses to be held during the lunch workshops. The SICOT head office has worked very hard together with the local organising committee to develop this exceptional programme. We thank Thomas Trc, the Congress President and Votech Havlas, the Local Scientific Chair, for their involvement and their arrangement of a series of memorable and attractive social events to complement the scientific programme. As the Czech Republic is our guest, I should honour, among others, such great national orthopaedic surgeons as Prof. Jan Zahradnicek and his work on congenital hip dysplasia who was a founding member of SICOT in 1929 and was followed by Oldrich Cech, his last pupil and National Delegate of SICOT from 1990 to 2000. He was also for many years the Editor in Chief of the Acta Chirurgiae Orthopaedicae et Traumatologiae Cechoslovaca. The SICOT Congress and our journal International Orthopaedics with their contribution at the sharp edge of scientific knowledge offer many countries a unique international forum to exchange and discuss their scientific contribution at the highest scientific level. Be part of these world events in orthopaedic surgery and traumatology.

Ostéoporose postménopausique : le point sur sa prise en charge

The current management of osteoporosis is based on several keypoints. The first critical step is to identify patients at high risk of fragility fracture, especially those who already sustained a first fracture, but still not often treated. Evaluating fracture risk includes not only bone-mineral density measurement and age, which are the two main risk factors, but also other clinical risk factors. Treatment decision is then based on estimated level of absolute fracture risk over 10 years. In fact, the main goal of postmenopausal osteoporosis treatment is to reduce this risk of fragility fracture. Treatment choice is based both on drug properties demonstrated by clinical trials and the specific fracture risks of each patient. In addition, it is important to identify whether patients are at risk of vertebral fractures or else at risk of vertebral and nonvertebral fractures. Duration of treatment is at least four to five years after which individual-fracture risk has to be reevaluated. As in many other chronic disease treatments, adherence to therapy is poor and has to be carefully assessed by all health-care professionals.

Treatment of osteoporotic ovariectomized rats with 24,25(OH)2D3

Antiresorptive therapeutic regimens are the mainstay of current management of osteoporosis. Treatments that are promoting new bone formation are less available and less affordable. Previous studies have suggested that 24,25(OH)(2)D(3) could enhance bone formation. The effect of 24,25(OH)(2)D(3) on bone formation in ovariectomized osteopenic rats (OVX) was evaluated in this study. Mature Sabra rats were divided into two groups: sham-operated and OVX. Three months after surgery the OVX and sham-operated rats were divided into the following subgroups: (1) sham rats injected with vehicle, (2) sham rats injected with 24,25(OH)(2)D(3), (3) OVX rats injected with vehicle, and (4) OVX rats injected with 24,25(OH)(2)D(3). After 2 weeks' treatment, histomorphometry of the right tibiae was performed. Ovariectomy resulted in a decrease in total bone volume (TBV/TV) and in bone formation (BFR/BS), P < 0.005 and P < 0.05 respectively, when compared with the sham-operated rats. Beside the decrease in TBV and BFR, the OVX rats showed an increase in osteoclastic bone resorption (P < 0.001 vs. sham). Administration of 24,25(OH)(2)D(3) was followed by an increase in all static and dynamic bone-forming parameters. The TBV/BV (P < 0.025), osteoblast surface (Ob.S/BS) (P < 0.001), as well as the BFR/BS (P < 0.005), increased in the OVX-treated group when compared with the OVX-untreated and sham-operated rats. This increment in bone formation was associated with a decrease in bone resorption (P < 0.001 in OVX-treated vs. OVX-untreated rats). This study shows that 24,25(OH)(2)D(3) may be of benefit in experimental osteopenia following ovariectomy, both by suppressing osteoclastic hyperactivity and by stimulating bone formation.