New Drugs

Of three new therapies on the horizon in the last edition, abaloparatide (brand name Tymlos) and romosozumab (brand name Evenity) have been approved by the FDA for the treatment of osteoporosis.

Abaloparatide is a novel 34-amino acid peptide, which is a selective activator of the parathyroid hormone receptor type 1 signaling pathway.1 In Phase 3 studies, women were randomized to receive abaloparatide, teriparatide, or placebo. Compared to placebo, women randomized to abaloparatide had a 3.4% increase in BMD at the total hip, 2.9% increase at the femoral neck, and 9.2% at the lumbar spine.2 These increases were observed earlier than in the teriparatide group. Abaloparatide also reduced vertebral fracture and nonvertebral fracture risk by 86% and 43%, respectively.2 Abaloparatide is effective at increasing BMD and reducing fracture risk at all levels of baseline risk (i.e., baseline BMD score, prevalent fracture status, prior fracture status, age)3 and even in the oldest old.4
 
Romosozumab, FDA approved April 9, 2019, is a monoclonal antibody to sclerostin. Sclerostin is produced by osteocytes and inhibits bone formation while enhancing bone resorption. The pivotal Phase 3 study showed that 1-year of romosozumab administered monthly compared to placebo increased BMD at the lumbar spine by 13%, and reduced the risk of new vertebral fractures by 73%.5 In an additional study that compared romosozumab to alendronate, the risk of new vertebral fracture was 48% lower in the group randomized to romosozumab followed by alendronate than in the group who were randomized to alendronate and continued alendronate throughout the study.6 This study, but not a larger one against placebo, found a higher rate of adverse cardiovascular safety outcomes, including cardiac ischemic events and cerebrovascular events in the romosuozumab group.6

Secondary Fracture Prevention

Having one fragility fracture increases the risk for a second fragility fracture, with estimates ranging from 37% at the same site to nearly seven-fold for different sites.7^,8^,9^,10 Thus, secondary fracture prevention is important clinically and a major emphasis of the American Society for Bone and Mineral Research (ASBMR).

Programs and Services to Help Prevent Secondary Fractures 

Many tools have been created to assist in secondary fracture prevention, with the Fracture Liaison Service (FLS) programs the most well-known. FLS programs have been shown to be successful in many European countries and have become international platforms for secondary fracture prevention. In the US, the first FLS programs were initiated within the Kaiser Permanente health system, a closed health network. In 2014, a simulation analysis estimated the cost effectiveness of FLS programs if initiated in the traditional US open-healthcare system.11 This study projected that over the remaining life span (mean of 8.6 years) of 10,000 men and women who sustained an index hip fracture, there would be an estimated 5,579 subsequent fractures, including 1,958 hip, 453 distal forearm, 998 vertebral, and 2,170 fractures of other sites. Implementation of a universal FLS was projected to reduce the rates of subsequent hip fracture by 109 per 10,000 persons, 21 fewer spine fractures, 5 fewer distal forearm fractures, and 17 fewer other osteoporotic fractures. The reduction in fracture rate was associated with a $66,879 reduction in costs and an increase in quality adjusted life expectancy (QALE) of 37.4 years for every 10,000 patients.10

This information led groups, including the National Osteoporosis Foundation (NOF) and the American Orthopaedic Association’s “Own the Bone” (AOA-OTB) program, to promote FLS training in the US. The NOF’s Fracture Prevention Central (FPC) website, an online toolkit accessible to the public, includes tools and resources for those interested in starting an FLS program, as well as guidance to hospital administrators, affordable healthcare organizations, and health insurers on how to make a financial business case for implementing a FLS program at their location. NOF also has the FLS Model of Care Training Program  designed to help doctors, nurse practitioners, physician assistants, registered nurses, and other healthcare professionals improve the care management of post-fracture patients and navigate the complicated coordination of the care process across hospitals, medical offices and multiple medical specialties through the application of best practices. The program is designed as a self-paced, on-demand webinar series. Participants can choose to complete individual FLS sessions or complete all sessions and receive the FLS Certificate. The goal of the program is to ensure that fracture patients receive appropriate osteoporosis testing, diagnosis, treatment and ongoing support after they leave the hospital.

Own the Bone program is a national post-fracture, systems-based, multidisciplinary fragility fracture prevention initiative. Its Web-based program and 10 prevention measures transform the way hospitals treat fracture patients. The ultimate goal is to change physician and patient behavior to reduce incidence of future fractures and positively impact osteoporosis treatment. The program conducts educational webinars and symposiums addressing nutrition counseling, physical activity counseling, lifestyle counseling, pharmacotherapy recommendations, BMD testing, and communication about bone health and additional risk factors. Own the Bone also has an extensive registry, which is consistent with the demographics of the general population of those with osteoporosis. Bone health experts establish standards of care through a medical advisory board for Own the Bone.

Both NOF and AOA-OTB have partnered with Project ECHO to disseminate FLS training through the ECHO platform, an initiative of the University of New Mexico, which uses case-based clinical discussions in a spoke and hub manner to disseminate information. The ECHO model™ breaks down the walls between specialty and primary care by linking expert specialist teams at an academic ‘hub’ with primary care clinicians in local communities – the ‘spokes’ of the model. In addition to the University of New Mexico, the ECHO platform is used by MNI Great Lakes ECHO in MI. To learn more about joining the Bone Health ECHO® program, click here.

The International Osteoporosis Foundation has the “Capture the Fracture” program, which has created the Best Practice Framework, an international benchmark for FLS programs, that includes 13 globally-endorsed standards:

1     Patient identification,
2     Patient evaluation,
3     Post fracture assessment timing,
4     Vertebral fracture,
5     Assessment guidelines,
6     Secondary causes of osteoporosis,
7     Fall prevention,
8     Multifaceted health and lifestyles risk-factor assessment,
9     Medication initiation,
10    Medication review,
11    Communication strategy,
12    Long-term management, and
13    Creating a database.

The American Society for Bone and Mineral Research (ASBMR) has created the Secondary Fracture Prevention Initiative, a coalition of bone health experts, including healthcare professionals and patient advocates, dedicated to reducing the number of avoidable second fractures in individuals with osteoporosis. The Initiative, with consensus from a broad multi-stakeholder coalition, has developed five fundamental clinical recommendations and seven additional recommendations for clinical care for women and men, age 65 years or older, with a hip or vertebral fracture. They are directed to all healthcare professionals who participate in the care of these patients, with the goal of reducing secondary fractures.

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• 2. a. b. Miller PD, Hattersley G, Riis BJ, et al. Effect of Abaloparatide vs Placebo on New Vertebral Fractures in Postmenopausal Women With Osteoporosis: A Randomized Clinical Trial. JAMA. 2016;316(7):722-733.
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• 10. a. b. Balasubramanian A, Zhang J, Chen L, et al. Risk of subsequent fracture after prior fracture among older women. Osteoporos Int. 2019;30(1):79-92. doi: 10.1007/s00198-018-4732-1. Epub 2018 Nov 19.
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