Monitoring Osteoporosis Therapy

Transcription

1 Monitoring Osteoporosis Therapy SUZANNE MORIN DEPT OF MEDICINE, DIVISION OF GENERAL INTERNAL MEDICINE, MUHC CENTRE FOR OUTCOMES RESEARCH AND EVALUATION, RI MUHC November 2017

2 Conflict of Interest Disclosures Research Grants (investigator initiated) paid to Research Institute MUHC Amgen Merck

3 Objectives 1. Discuss benefits and harms associated with anti-osteoporosis therapy 2. Discuss benefits of monitoring with sequential bone mineral density tests and bone turnover markers in the setting of osteoporosis therapy 3. List clinical markers that may guide monitoring of long term bisphosphonate therapy

4 Osteoporosis is a Disorder of Bone Strength Research Institute of the McGill University Health Center

5 Bone Strength Biomechanical, biological and genetic factors Bone Quality + Bone Density + Bone Geometry Bone mineral content Bone turnover Activation Frequency Damage accumulation Quality of material Bone diameter Cortical thickness Limb alignment Bone Strength Adapted from R.Rizzoli 2005

6 Muscle-Bone Cross Talk

7 Mechanical Failure: Fracture Hernandez CJ et al, JBMR 2017

8 Clinical Diagnosis of Osteoporosis National Bone Health Alliance Working Group T-scores 2.5 by BMD testing Low trauma hip fracture (regardless of BMD) Vertebral, proximal humerus, pelvis fractures with low BMD FRAX scores with 20% (major fractures) or 3 % (hip fractures) 10-year fracture risk Siris ES et al Osteoporos Int 2014; 25:

9 Osteoporosis->Fractures Increased risk of Hospitalization Institutionalization Subsequent fractures Decreased quality of life Death Economic burden on healthcare system

10 First Line Therapies for Fracture Prevention Papaioannou CMAJ 2010

11 Antiresorptive agents: Bisphosphonates and Denosumab Inhibit osteoclastic activity Decrease BTM Increase BMD Reduce Fractures Generally well tolerated Associated with Osteonecrosis of the Jaw Atypical Femur Fractures Bisphosphonates: slow offset Denosumab: rapid offset

12 Anabolic agent: Teriparatide Activates osteoblastic activity Increase BMD Reduce Fractures Generally well tolerated rapid offset Associated with: Hypercalcemia Hyperuricemia BlackBox warning: Osteosarcoma *approved for max 24 months

13 Monitoring Adherence to management plan (Exercise) Adverse effects Falls Fractures Bone Mineral Density no RCT data on how often to monitor BMD during treatment Look for significant change (3-5% lumbar spine, 3-9% Femoral Neck) Bone Turnover Markers May be useful in selected cases (?treatment failure) Other measures? 25 hydroxy-vitamin D, PTH, serum protein electrophoresis : only in selected cases

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15 Cumulative Risk of Fracture Risk Leslie WD et al, 2016 Annals Internal Medicine

16 Bone Turnover Markers Antiresorptive therapy: BTMs: resorption Anabolic therapy: BTMs: formation

17 Monitoring of long term use of bisphosphonates 5 years or more Concern: Atypical Femur Fracture: RARE Characteristics that are found to be more frequent in patients with AFF Thigh or groin pain- prodromal symptom of AFF Use of concomitant medications such as glucocorticoids, PPI Femur bowing, varus at the hip

18 Duration of use of osteoporosis treatment Anabolic therapy (teriparatide) maximum 24 months (rapid offset) Antiresorptive therapy Bisphosphonates: 3 to 5 years and then reassess? Drug holiday (slow offset) Denosumab: No prescribed duration- Avoid stopping (rapid offset) HRT: as per menopausal symptom management recommendations (rapid offset) SERM: no prescribed duration (rapid offset)

19 Key Messages Fracture prevention management plan includes exercise and fall prevention strategies Once pharmacotherapy is initiated, monitoring should include: Documentation of adherence to management plan Inquiry re adverse events and concerns BMD 2 years following initiation of therapy, then at 5 years, if all stable No more frequently than 18 months BTMs and other serum measures in selected cases at the time of BMD Long term bisphosphonate use (5 years or more) is appropriate in patients at high risk of fractures o Monitor thigh groin pain Educational material available on Osteoporosis Canada website Canadian Osteoporosis Patient Network