Category: Calcium/Bone Disorders
In the ACTIVE phase 3 study (NCT01343004), 18 months (M) of abaloparatide (ABL) treatment significantly increased bone mineral density (BMD) and reduced the risk of new vertebral, nonvertebral, clinical, and major osteoporotic fractures vs placebo (PBO); findings were generally consistent in a post hoc analysis of women with type 2 diabetes mellitus (T2DM) in ACTIVE. Women receiving ABL or PBO in ACTIVE were offered enrollment in the ACTIVExtend extension study in which both groups received 24M open-label alendronate (ALN) 70 mg weekly for a total of 43M (18M ABL or PBO, 1M for reconsent, and 24M ALN). The objective of this post hoc analysis was to evaluate the efficacy of ABL followed by ALN (ABL/ALN) vs PBO/ALN in the subgroup of patients with T2DM.
Methods : A total of 1,139 patients (558, ABL/ALN and 581, PBO/ALN) were enrolled in ACTIVExtend. Patients with T2DM were identified by review of medical history records. Prespecified endpoints including BMD, new vertebral, nonvertebral, clinical, and major osteoporotic fractures were assessed over the 43M period. New vertebral fracture incidence was evaluated using the mITT population, other endpoints were evaluated using the ITT population.
A total of 125 patients with T2DM were identified (ABL/ALN n = 61, PBO/ALN n = 64) [median age: 70 years; range: 55-82 years; mean femoral neck (FN) T-score: -2.26]. At 43M, 0% of ABL/ALN and 3.2% of PBO/ALN patients experienced a new vertebral fracture (p = NS). Kaplan-Meier estimated incidence were 3.4% ABL/ALN and 10.1% PBO/ALN for nonvertebral, 6.7% ABL/ALN and 10.1% PBO/ALN for clinical, and 1.7% ABL/ALN and 6.9% PBO/ALN for major osteoporotic fractures (p = NS, all comparisons). At 43 months, significant (p < 0.0001) increases in BMD from baseline were observed for ABL/ALN vs PBO/ALN at the total hip (mean change 6.3% vs 1.7%), femoral neck (4.7% vs 1.0%), and lumbar spine (15.9% vs 6.9%).
Discussion : Among the subgroup of women with osteoporosis and T2DM in ACTIVExtend, ABL followed by ALN resulted in numerical reductions in the risk of vertebral, nonvertebral, clinical, and major osteoporotic fractures, and significant improvements in BMD compared with PBO followed by ALN. Results are consistent with those previously reported in the overall ACTIVExtend population.
Conclusion : This post hoc analysis suggests that ABL followed by ALN may provide a valuable treatment sequence for women with postmenopausal osteoporosis and T2DM at high risk for fracture.
Ruban Dhaliwal– Assistant Professor of Medicine, SUNY Upstate Medical University, New York
Bruce Mitlak– Vice President, Clinical Development, Radius Health, Inc., Waltham, MAA
Lorraine Fitzpatrick– Chief Medical Officer Emeritus, Radius Health, Inc.
Yamei Wang– Senior Director, Biostatistics, Radius Health, Inc., Waltham, MA
Ann Schwartz– Associate Professor, UCSF School of Medicine, San Francisco, CA
Paul Miller– Medical Director, Corado Center for Bone Research, Lakewood CO
Robert Josse– Professor of Medicine, Saint Michael’s Hospital, Toronto, ON, Canada
Assistant Professor of Medicine
SUNY Upstate Medical University, New York
Education & Experience
Residency: North Shore-Long Island Jewish Health System
Fellowship (Endocrinology, Diabetes and Metabolism): SUNY Upstate Medical University
An Observational, Longitudinal, Prospective, Long-Term Registry of Patients with Hypophosphatasia. Protocol ALX-HPP-501.
Paradighm (Physicians Advancing Disease Knowledge in Hypoparathyroidism): A Natural History Registry for Patients with Chronic Hypoparathyroidism
Certifications & Licensure
American Board of Internal Medicine: Certified in Endocrinology, Diabetes and Metabolism
American Board of Internal Medicine: Certified in Internal Medicine - NY State Medical License
Vice President, Clinical Development
Radius Health, Inc., Waltham, MAA
Bruce completed his undergraduate education at Vassar College in Biochemistry and was elected to Phi Beta Kappa (1981). He graduated from the University of Connecticut School of Medicine and was elected to Sigma Xi (1985).
He completed his residency training in Internal Medicine at the New England Deaconess Hospital and a fellowship in Endocrinology and Metabolism at the Massachusetts General Hospital (1991). He then served as a member of the Endocrine Unit focused on clinical and basic aspects of disorders of mineral metabolism. He was a tutor and lecturer at Harvard Medical School where he was an Assistant Professor of Medicine. More recently he was a lecturer at the Indiana University School of Medicine. Bruce authored more than 75 original articles and chapters including publications which have appeared in the New England Journal of Medicine and JAMA.
Bruce retired as a Distinguished Medical Fellow at Eli Lilly and Company where he served for more than two decades supporting the development, registration and commercialization of novel treatments for women’s health and osteoporosis including Evista and Forteo.
Currently Bruce is a Distinguished Medical Fellow and VP of Clinical Development at Radius Health.
Chief Medical Officer Emeritus
Radius Health, Inc.
Dr. Lorraine A. Fitzpatrick completed her undergraduate education at Wellesley College with honors in Molecular Biology. She graduated from the Pritzker school of Medicine at the University of Chicago where she received an award for her research. She completed her residency training in Internal Medicine at Columbia-Presbyterian Medical Center in New York. Dr. Fitzpatrick trained in Mineral Metabolism and Endocrinology at the National Institute of Diabetes, Digestive, Arthritis and Kidney Disorders at the National Institutes of Health. Dr. Fitzpatrick joined the staff at the Mayo Clinic and rose to the rank of Professor of Medicine. Dr. Fitzpatrick has held many national and international positions. She has published over 250 papers in the field of mineral metabolism. She has received many awards for her research from the ASBMR, The Endocrine Society, the AFCR and was elected to the American Society for Clinical Investigation. She has been an editor or on the editorial boards of multiple publications including Endocrinology, JBMR, Mayo Clinic Proceedings, Bone and Mineral and the Year Book of Endocrinology, to name a few. She has held multiple positions including chair of two study sections at NIH and a member of the Board of Directors for the Office of Women’s Health at NIH.
Dr. Fitzpatrick joined Amgen where she worked on drug development and rose to the title of Global Scientific Director in osteoporosis. Dr. Fitzpatrick then worked in drug development at GlaxoSmithKline as the Medicine Development Leader, leading an international team representing multiple disciplines including clinical development, safety, regulatory, manufacturing, commercial, operations, epidemiology, and global health outcomes. In 2015, Dr. Fitzpatrick joined Radius Health, Inc., as Chief Medical Officer where she leads Clinical Affairs, Medical Affairs and Pharmacovigilance. In 2018, she took the position of Chief Medical Officer Emeritus to focus on abaloparatide and new indications.
Senior Director, Biostatistics
Radius Health, Inc., Waltham, MA
Yamei Wang has worked in the pharmaceutical industry as a biostatistician for about ten years. She holds a master degree in biostatistics and Ph.D. degree in health service with minor on health policy. She has published several research articles as a coauthor on the peer review journals in recent years.
UCSF School of Medicine, San Francisco, CA
Dr. Schwartz's research focuses on the epidemiology and etiology of fractures, osteoporosis, and falls in older adults with diabetes. She is currently the PI of ACCORD BONE, an ancillary study to the ACCORD trial in older adults with type 2 diabetes, examining the effects of intensive glycemic control and TZD use on skeletal health. She is pursuing investigations into the reasons for reduced bone strength in type 2 diabetes, including the role of marrow fat, advanced glycation endproducts, and cortical porosity. Dr. Schwartz serves as the Director of the San Francisco Coordinating Center DXA Quality Assurance Group.
Corado Center for Bone Research, Lakewood CO
Dr. Paul D. Miller, MD, FACP is an internationally recognized physician specializing in research on metabolic bone disease. He is widely considered a leading authority on bone biology and the prevention and treatment of metabolic bone disorders, including osteoporosis.
It was during Dr. Miller’s time as a practicing Nephrologist that he developed an intense passion around metabolic bone disease. This interest led Dr. Miller to open the Colorado Center for Bone Research in 1994. Dr. Miller is the Medical Director at the CCBR—which is acknowledged as a top facility for the diagnosis and treatment of metabolic bone disease. He is also an avid researcher and scholar. He focuses on the treatment of osteoporosis in postmenopausal women and he is the principal investigator in a number of clinical trials evaluating the safety and efficacy of current and potential therapies.
Dr. Miler is the author and co-author of more than 300 peer-reviewed publications and has also authored or coauthored over 50 textbooks and chapters. His insights and thought leadership have made him a media resource and sought-after speaker. He lectures widely at regional, national and international levels to physicians and at scientific conferences.
Professor of Medicine
Saint Michael’s Hospital, Toronto, ON, Canada
I have obtained peer reviewed and non-peer reviewed grants (mostly Phase II and III pharmaceutically funded multi-centre national and international studies) as principal, co-principal or co-investigator. These studies have investigated the effects of various new drugs on diabetes control, hyperlipidemia and prevention or treatment of diabetes complications. I have been particularly interested in the nutritional management of diabetes with other colleagues in the division (Jenkins, Vuksan, Wolever): we have promulgated the concept of the glycemic index of foods and the importance of meal frequency as therapeutic principles. Our more recent studies have moved into the area of disease prevention, e.g. diabetes, cardiovascular disease and osteoporosis using different nutraceuticals as well as drugs. We have also been investigating the potential efficacy of herbal and alternative medicine remedies, e.g. ginseng, Konjac-mannan.
Our group has been involved in a number of national and international osteoporosis studies in epidemiology, as well as phase III clinical drug trials. We collaborate widely with the Women’s Health Centre, rheumatology, physiatry, orthopedics and other disciplines within the hospital and city-wide. I am the director of the Toronto Centre of the CIHR-funded Canadian Multicentre Osteoporosis Study (CaMOS). The osteoporosis centre (of which I am the director) is a focus for clinical and epidemiologic research, as well as graduate and postgraduate education and general patient care.