Drug Holidays From Osteoporosis Meds Linked to More Broken Bones

MedicalResearch.com Interview with:
“Just a hairline fracture...” by Gloria Bell is licensed under CC BY 2.0Brittany Bindon, MD

Department of Internal Medicine
University of Chicago
Chicago, Illinois

MedicalResearch.com: What is the background for this study?

Response: Bisphosphonates are commonly used in the treatment of osteoporosis, however, they have been associated with rare, severe side effects such as osteonecrosis of the jaw and atypical femoral fractures.

As a result, bisphosphonate drug holidays have become common in clinical practice though currently, there are minimal data on the safe duration of these drug holidays. We sought to further characterize the clinical and laboratory parameters associated with increased fracture risk in patients on bisphosphonate drug holiday.

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Osteoporosis Drug Has Potential To Fight Triple Negative Breast Cancer

MedicalResearch.com Interview with:
Chenfang Dong, Ph.D & M.D.
Professor
Department of Pathology and Pathophysiology
Zhejiang University School of Medicine, 

MedicalResearch.com: What is the background for this study? What are the main findings? 

Response: Basal-like breast cancer (BLBC), which generally falls into the triple-negative breast cancer subtype, is associated with a poor clinical outcome due to few treatment options and poor therapeutic response; thus there is a pressing need to elucidate the determinants of aggressiveness in BLBC and identify potential therapeutic targets for this challenging disease.

By analyzing gene expression profiles of breast cancer in multiple publicly available datasets that contain over 5000 cases, we have identified that UDP-galactose ceramide galactosyltransferase (UGT8), a key enzyme in the sulfatide biosynthetic pathway, promotes BLBC progression by activating sulfatide-αVβ5 axis.

Importantly, we identify that zoledronic acid (ZA), a marketed drug for treating osteoporosis and bone metastasis, is a direct inhibitor of UGT8, which has the potential to become a valuable targeted drug for treating Basal-like breast cancer.  Continue reading

Later Puberty Linked To Lower Adult Bone Density

MedicalResearch.com Interview with:

Dr. Cousminer

Dr. Cousminer

Diana L. Cousminer, PhD
Division of Human Genetics
Children’s Hospital of Philadelphia
Philadelphia, PA 19104

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Osteoporosis is a significant public health burden, with origins early in life. Later puberty and lower adolescent bone mineral density are both risk factors for osteoporosis.

Geneticists have identified hundreds of genetic variants across the genome that impact pubertal timing, and we found that collectively this variation also plays a role in bone mineralization during adolescence. Additionally, we found that later puberty caused lower adult bone density.

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Exercise, Vision Testing and Osteoporosis Evaluation Are Keys To Fall Prevention

MedicalResearch.com Interview with:

Andrea C. Tricco PhD, MSc Scientist and Lead of the Knowledge Synthesis Team Associate Professor Dalla Lana School of Public Health, University of Toronto Associate Editor Journal of Clinical Epidemiology, BMC Medical Research Methodology, Systematic Reviews

Dr. Tricco

Andrea C. Tricco PhD, MSc
Scientist and Lead of the Knowledge Synthesis Team
Associate Professor Dalla Lana School of Public Health, University of Toronto
Associate Editor Journal of Clinical Epidemiology, BMC Medical Research Methodology, Systematic Reviews

MedicalResearch.com: What is the background for this study?

Response: Falls are the leading cause of injury among older adults and account for $2 billion in direct health-care costs annually ($31 billion in costs to Medicare in the United States in 2012). We aimed to determine which types of fall-prevention programs may be effective for reducing falls in older people.

MedicalResearch.com: What are the main findings?

Response: Exercise, along with vision assessment and treatment, as well as an assessment and possible modification of a person’s living environment, reduced the risk of injurious falls by 23% compared to usual care.

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New Approach Could Lead To Osteoporosis Drugs With Fewer Side Effects

MedicalResearch.com Interview with:

Dieter Bromme, Ph.D. Professor and Canada Research Chair The University of British Columbia Faculty of Dentistry  Vancouver, BC

Dr. Bromme

Dieter Bromme, Ph.D.
Professor and Canada Research Chair
The University of British Columbia Faculty of Dentistry
Vancouver, BC

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Every three seconds somebody will fracture a bone because of osteoporosis. Several treatments are available to slow down bone loss but all of them have shortcomings ranging from poor bone quality to various side effects. Thus new treatment strategies and novel drug targets are needed that promise efficacy without significant adverse reactions.

One of the novel promising targets was cathepsin K, a protease solely responsible for the degradation of our organic bone matrix. Major efforts and funds were spent by the pharmaceutical industry to develop potent and selective cathepsin K inhibitors. These inhibitors were highly effective in preserving bone in clinical trials. Despite the good news, cathepsin K inhibitors were never approved because of various non-skeletal side effects. We hypothesized that these side effects are not caused by off-target effects (drugs react with undesired targets) but by on-target effects. Most drugs that target enzymes are active site-directed compounds and thus will stop the entire activity of the target enzyme. If the target is a multifunctional enzyme, safety problems are preprogrammed. Based on our studies to understand the molecular mechanism of collagen degradation by cathepsin K, we developed the concept of ectosteric enzyme inhibition, which allowed us to identify highly selective collagenase inhibitors of this protease.

In our study, we used a red sage-derived small molecule that selectively blocked the collagenase activity of cathepsin K and thus consequently bone degradation in an osteoporosis mouse model without affecting other known functions of the protease. The crucial difference might be that the red sage inhibitor did not block the cathepsin K-mediated degradation of TGF-ß1, a growth factor involved in fibrotic pathologies described in the clinical trials. TGF-ß1 degradation is blocked by these inhibitors and thus accumulates in tissues, causing fibrosis.

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Dabigatran is Associated With a Lower Risk of Osteoporotic Fractures Compared to Warfarin

MedicalResearch.com Interview with:
Wallis CY Lau BSc

Centre for Safe Medication Practice and Research
Department of Pharmacology and Pharmacy
Li Ka Shing Faculty of Medicine
The University of Hong Kong

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Warfarin is a vitamin K antagonist (VKA) oral anticoagulant used for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF), a common heart rhythm disorder. It works by interfering with vitamin K-dependent reactions in the process of blood clot formation. As these reactions also play a role in bone mineralization, there is concern that warfarin use may be linked with osteoporotic fracture. Despite the concerns for fracture risk, warfarin had been an inevitable treatment choice for over 50 years as there were no other alternatives available.

Dabigatran is the first non-VKA oral anticoagulant (NOAC) approved for use in patients with NVAF. Recently, an animal study reported that use of dabigatran is associated with a better bone safety profile compared to warfarin in rats, suggesting a potential for a lower risk of osteoporotic fractures over warfarin. However, the actual risk of osteoporotic fractures with dabigatran use in human remains unclear. Therefore, we conducted a population-based cohort study to compare the risk of osteoporotic fractures in patients with NVAF treated with dabigatran and warfarin.

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Regular, Long-term Resistance Training or Jump-Training Increases Bone Mass

MedicalResearch.com Interview with:

Pamela S. Hinton, Ph.D. Associate Professor & Director of Graduate Studies Department of Nutrition and Exercise Physiology Columbia MO 65211

Dr. Hinton

Pamela S. Hinton, Ph.D.
Associate Professor & Director of Graduate Studies
Department of Nutrition and Exercise Physiology
Columbia MO 65211

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: This study builds on our previous work showing that weight-bearing, high-impact physical activity throughout the lifespan is associated with greater bone mass in men.  We previously conducted a 12-month randomized trial of the effectiveness of resistance training versus jump training to increase bone mass in men with low bone density of the hip or lumbar spine.

The current study is a follow up study investigating how exercise might work to increase bone mass.

The main findings are that exercise reduced circulating levels of a bone protein that inhibits bone formation (sclerostin) and increased levels of insulin-like growth factor-I (IGF-I), a hormone with osteogenic effects.

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Compared To Other Blood Pressure Medications Diuretics Have Bone Protective Effect

MedicalResearch.com Interview with:

Joshua I. Barzilay, MD Kaiser Permanente of Georgia Duluth, GA 30096

Dr. Joshua I. Barzilay

Joshua I. Barzilay, MD
Kaiser Permanente of Georgia
Duluth, GA 30096

MedicalResearch.com: What is the background for this study?

Response: Hypertension (HTN) and osteoporosis (OP) are age-related disorders. Both increase rapidly in prevalence after age 65 years. Prior retrospective, post hoc studies have suggested that thiazide diuretics may decrease the risk of osteoporosis. These studies, by their nature, are open to bias. Moreover, these studies have not examined the effects of other anti HTN medications on osteoporosis.

Here we used a prospective blood pressure study of ~5 years duration to examine the effects of a thiazide diuretic, a calcium channel blocker and an ACE inhibitor on hip and pelvic fractures. We chose these fractures since they are almost always associated with hospitalization and thus their occurrence can be verified.

After the conclusion of the study we added another several years of follow up by querying medicare data sets for hip and pelvic fractures in those participants with medicare coverage after the study conclusion.

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Menopausal Hormone Therapy Benefits Bone Health For Several Years After Discontinuation

MedicalResearch.com Interview with:

Dr Georgios Papadakis FMH, Médecin InternenMédecin assistant Service d'endocrinologie, diabétologie et métabolisme Lausanne

Dr Georgios Papadakis

Dr Georgios Papadakis
FMH, Médecin InternenMédecin assistant
Service d’endocrinologie, diabétologie et métabolisme
Lausanne

MedicalResearch.com: What is the background for this study?

Response: This study was mainly motivated by the absence of available data on the effect of menopausal hormone therapy (MHT) on bone microarchitecture, as well as contradictory results of previous trials regarding the persistence of a residual effect after MHT withdrawal.

We performed a cross-sectional analysis of 1279 postmenopausal women aged 50-80 years participating in OsteoLaus cohort of Lausanne University Hospital. Participants had bone mineral density (BMD) measurement by dual X-ray absorptiometry (DXA) at lumbar spine, femoral neck and total hip, as well as assessment of trabecular bone score (TBS), a textural index that evaluates pixel grey-level variations in the lumbar spine DXA image, providing an indirect index of trabecular microarchitecture.

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Clinical Practice Guidelines For Diagnosis and Treatment of Postmenopausal Osteoporosis

MedicalResearch.com Interview with:

Pauline Camacho, MD, FACE Professor, Endocrinology Director, Loyola University Osteoporosis and Metabolic Bone Disease Center, Fellowship Program Director, Endocrinology, Medical Director, Osteoporosis Center

Dr. Pauline Camacho

Pauline Camacho, MD, FACE
Professor, Endocrinology
Director, Loyola University Osteoporosis and Metabolic Bone Disease Center, Fellowship Program Director, Endocrinology, Medical Director, Osteoporosis Center

MedicalResearch.com: What is the background for this report? What is the prevalence and significance of osteoporosis in US women?

Response: Osteoporosis is widely prevalent and is increasing in prevalence not only in the US but also around the world. 10.2 million Americans have osteoporosis and that an additional 43.4 million have low bone mass. More than 2 million osteoporosis-related fractures occur annually in the US, more than 70% of these occur in women ( from National Osteoporosis Foundation (NOF) estimates).

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