AACE Post-Menopausal Osteoporosis Guidelines Educational Objectives

Transcription

1 AACE Post-Menopausal Osteoporosis Guidelines 2015 Pauline Camacho, MD, FACE Steven M. Petak MD, JD, MACE, FCLM Educational Objectives Discuss AACE guidelines related to the prevention of osteoporosis Review the approach to determining those that can most benefit from osteoporosis therapy in the AACE guidelines Differentiate treatment options and initiate individualized treatment regimens for management of osteoporosis in the guidelines 1

2 It ain't what you don't know that gets you into trouble. It's what you know for sure that just ain't so. Mark Twain For full evidence based guideline see: 2

3 Measures to Prevent Bone Loss R1. Maintain adequate calcium intake R2. Maintain adequate vitamin D intake R3. Limit alcohol to 2 servings daily R4. Limit caffeine intake R5. Avoid or stop smoking R6. Maintain active lifestyle including weight bearing exercise at least 30 minutes daily 2015 Discussion Points: Bone Health PMO Vitamin D Measure 25-OH vitamin D in those at risk for insufficiency Preferable range 25-OHD : 30 ng/ml to 60 ng/ml Supplementation if needed: generally in range of IU daily with higher amounts in some patients Calcium Counsel on adequate dietary intake of calcium about 1200 mg daily Exercise Active lifestyle, weight bearing and balance exercises Refer PT and OT as needed (Petak SM and Watts NB) 3

4 Does Type of Calcium Make a Difference? Most preparations are calcium carbonate should be taken with food for maximal absorption, especially in elderly Calcium citrate slightly better absorbed, can be taken on an empty stomach but both carbonate and citrate should take with food to reduce oxalate absorption Better to split doses as % calcium absorption decreases with larger dose (limit about mg at at one time) Side effects such as bloating, constipation, nausea common especially in elderly (preparations with magnesium can counteract constipation) Food sources preferable Does Calcium Increase Vascular Risk? Calcium Supplements and Heart Events Meta-analysis reported increased risk of MI & cardiovascular events with calcium supplementation (Bolland, et. al, BMJ 2010) Additional analysis including 16,718 women (46%) not taking calcium supplements when WHI began found clinical MI or revascularization increased HR 1.16 (CI ) p = 0.04 Analysis of data from 8 other trials plus WHI 28,072 patients (8 trials plus WHI subgroup) Calcium with or without vitamin D versus placebo Cardiovascular events (MI or stroke) HR = 1.15 ( ) p = Bolland MJ et al. BMJ 2011;342:d2040 4

5 A study of > 9000 participants followed for 10 years found that postmenopausal women taking mg of supplemental calcium had a survival advantage (Langsetmo, JCEM 2013) Other studies found no effect of calcium supplements on CV risk (Lewis, JBMR 2011, Zhu, JBMR 2008, Hsia, Circulation 2007) Nonpharmacologic Measures in PMO Treatment R7. Maintain adequate protein intake R8. Use proper body mechanics R9. Consider use of hip protectors in individuals with high fall risk R10. Take measures to reduce fall risk R11. Consider referral to PT and OT 5

6 PMO: Screening R12. Women 65 years and older R13. Younger postmenopausal women at increased risk of fracture based on risk factors DXA to be considered based on fracture risk considerations 6

7 USPSTF 2010 Recommendations The USPSTF recommends screening for osteoporosis in women aged 65 years or older and in younger women whose fracture risk is equal to or greater than that of a 65-year-old white woman who has no additional risk factors. Rating B: The USPSTF recommends the service. There is high certainty that the net benefit is moderate or there is moderate certainty that the net benefit is moderate to substantial. USPSTF 2010 Recommendations Based on the U.S. FRAX tool, a 65-year-old white woman with no other risk factors has a 9.3% 10-year risk for any osteoporotic fracture. Although the USPSTF recommends using a 9.3% 10-year fracture risk threshold to screen women aged years, clinicians should also consider each patient s values and preferences and use clinical judgment when discussing screening with women in this age group. 7

8 What Does 9.3% Look Like? 50 year old, smoker, BMI < 21 kg/m 2, daily ETOH, parental history of hip fracture 55 year old with parental history of fracture 60 year old with BMI < 21 kg/m 2 with daily ETOH 60 year old smoker with daily ETOH PMO: Diagnosis R14. Use central DXA measurements R15. In absence of fracture, osteoporosis defined as a T-score -2.5 or below at spine, femoral neck, or total hip R16. Osteoporosis defined as presence of hip or spine fracture in absence of other bone conditions 8

9 2015 Discussion Point: Definition of Osteoporosis Definition to include: High fracture risk using FRAX country-specific threshold in a person with low bone mass or osteopenia? PMO: Evaluation R17. Evaluate for secondary osteoporosis R18. Evaluate for prevalent vertebral fractures Lateral spine imaging with x-ray studies or vertebral fracture assessment in patients with unexplained height loss, kyphosis, or suspected spine fractures 9

10 Secondary Causes: Often Occult Drugs Chronic Diseases Nutritional Conditions Endocrine Diseases or Metabolic Causes Glucocorticoids GnRH agonists Aromatase inhibitors Medroxyprogest erone acetate Phenytoin Excess thyroid Heparin Phenobarbital Lithium TZDs PPIs SSRIs Rheumatoid arthritis Myeloma and cancers COPD Organ Transplantation Renal tubular acidosis Mastocytosis Thalassemia Immobilization HIV Vitamin D deficiency Malabsorption Hypercalciuria Calcium deficiency Alcoholism Gastric/obesity surgery Chronic liver disease Malnutrition Homocysteine Hypogonadism Hyperparathyroidism Cushing syndrome Thyrotoxicosis Anorexia nervosa Hyperprolactinemia Porphyria Hypophosphatasia Type I DM Acromegaly Prevalence of Occult Secondary Osteoporosis No large, population-based studies; studies from referral centers vary by criteria for inclusion, extent of testing and definition of vitamin D deficiency Prevalence in studies which assessed urinary calcium and vitamin D: Women & men, varying ages % Post-hip fracture patients % Bone loss on pharmacologic therapy 6,7 > 50% 1 Deutschman H J Intern Med 252:389 2 Hayden ST Calcif Tissue Int 64:275 3 Ryan CS 2008 ASBMR abstract 4 Gabaroi DC 2010 Menopause 17:135 5 Edwards BJ 2008 Osteoporos Int 19:991 6 Lewiecki EM. J Bone Miner Res 2002;17(Suppl 1):S367 7 Geller JL, Endocr Pract 2008 Apr;14(3):293 10

11 Common Medications Possibly Associated With Increased Fracture Risk Proton-pump inhibitors (PPI s) hip fracture after long-term, high-dose therapy in observational studies 1 Selective-serotonin reuptake inhibitors (SSRI s) 2x risk fragility fracture seen with daily use 2 Thiazolidinediones (TZD s) risk peripheral fractures in post-menopausal women with type 2 diabetes on rosiglitazone compared to metformin or glyburide 3 1 Yang YX et al. JAMA 2006;296: Richards JB et al. Arch Int Med 2007;167: Kahn SE et al. Diabetes Care 2008;31: , Loke YK et al CMAJ 2009;180:32-9 What Testing Should be Done? ASBMR Recommendations Basic: CBC, chemistry panel, TSH, 25(OH)D, 24 hour urine calcium/creatinine Additional: E2, LH, FSH, prolactin, PTH, 1,25- OHD, 24 hour urine free cortisol, Iron/TIBC/ferritin, celiac testing, SPEP/UPEP, ESR/CRP, tryptase, bone turnover markers, transiliac bone biopsy (if low trauma fracture and negative evaluation) Cohen Adi, Shane E. Primer ASBMR 2009;

12 Importance of 24-hour Urine Calcium Effectively identifies both hypercalciuria and malabsorption when results fall outside normal values ( mg/day 1 ) Both disorders associated with higher rates of bone loss 1,2 Calcium deficiency associated with diminished or absent BMD response to therapy 2 Each condition requires a specific intervention for optimal patient management Spot urine calcium does not detect malabsorption 3 38% of new diagnoses would have been missed without 24 hour urine calcium results 14 1 Heaney RP, et al. Osteoporos Int 1999;9: Nieves JW 1998 Am J Nutr 67:182 3 Ciacci C, et al. Am J Gastroenterol. 1995;90: Tannenbaum C, et al. J Clin Endocrinol Metab. 2002;87: Who Needs Pharmacologic Therapy? R19. Those patients with a history of a fracture of the hip or spine R20. Patients without a history of fractures but with a T-score of -2.5 or lower R21. Patients with a T-score between -1.0 and -2.5 if FRAX 10 year major osteoporosis related fracture probability at 20% or more or hip fracture probability at 3% or more 12

13 US/NOF Thresholds: Major osteoporosis related fracture: 20% Hip fracture: 3% Apply clinical judgment!! What Drugs Can Be Used to Treat PMO? Use Drugs with Proven Antifracture Efficacy R22. Use alendronate, risedronate, zoledronic acid, and denosumab as first line therapy R23. Use ibandronate as a second line agent R24. Use raloxifene as a second or third line agent R25. Use calcitonin as the last line of therapy R26. Use teriparatide for patients with very high fracture risk or patients in whom bisphosphonate therapy has failed R27. Advise against the use of combination therapy Cost, improved efficacy not documented, safety 13

14 FDA-Approved Medications Drug PMO GIO Men Prevention Treatment Prevention Treatment Estrogen Calcitonin Alendronate Risedronate Ibandronate Zoledronic acid Raloxifene Denosumab Teriparatide Fracture Risk Reduction in PMO Medication Spine Hip Nonvertebral Estrogen Alendronate Risedronate Ibandronate Zoledronic acid Calcitonin Raloxifene Denosumab Teriparatide 14

15 2015 Discussion Points: Osteoporosis Medication Options Broad spectrum Alendronate, risedronate, zoledronic acid, denosumab Parenteral options if needed Denosumab, zoledronic acid, teriparatide Spine specific efficacy Ibandronate, raloxifene Combined denosumab and teriparatide achieves improved BMD response vs either agent alone but data for fracture risk are lacking. Strongly recommend antiresorptive therapy following teriparatide therapy 15

16 How is Treatment Monitored? R28. Obtain a baseline DXA, and repeat DXA every 1-2 years until stable. Continue follow-up every 2 years or at a less frequent interval R29. Monitor changes in spine or total hip BMD R30. Follow-up of patients should be in the same facility, with the same machine, and if possible, the same technologist R31. Bone turnover markers may be used at baseline to identify patients with high bone turnover and can be used to follow the response to therapy What is Successful Treatment of Osteoporosis? R32. BMD is stable or increasing and no fractures are present R33. For patients taking antiresorptive agents, bone turnover markers at or below the median value for premenopausal women are achieved R34. One fracture is not necessarily evidence of failure. Consider alternative therapy or reassessment for secondary causes of bone loss for patients who have recurrent fracture while receiving therapy 16

17 How Long Should Patients be Treated? R35. For treatment with bisphosphonates, if osteoporosis is mild, consider a drug holiday after 4-5 years of stability. If fracture risk is high, consider a drug holiday of 1-2 years after 10 years of treatment R36. Follow BMD and bone turnover markers during a drug holiday period and reinitiate therapy if BMD declines substantially, bone turnover markers increase, or a fracture occurs 2015 Discussion Points Consider a drug holiday after 3-5 years of stability in lower-risk patients and after 6-10 years in higher risk-patients. Teriparatide or raloxifene may be used during the bisphosphonate holiday in higher risk patients End of the holiday is based on individual patients 17

18 2015 Postmenopausal Osteoporosis Treatment Algorithm Lumbar spine or femoral neck or total hip T- score of 2.5, a history of fragility fracture, or high FRAX score** Screen for causes of secondary osteoporosis Correct calcium/vitamin D deficiency and address secondary causes Initiate pharmacologic therapy Education on lifestyle measures, fall prevention, benefits and risks of drugs No prior fragility fractures or Lower fracture risk ** Prior fragility fractures or higher fracture risk ** Alendronate, risedronate, zoledronic acid, denosumab Alternate therapy: Ibandronate, raloxifene, teriparatide To page 2 Teriparatide, denosumab, zoledronic acid Alternate therapy: Alendronate, risedronate, ibandronate, raloxifene To page 3 Continued from page 1 No prior fractures or Lower fracture risk Alendronate and risedronate, zoledronic acid, denosumab Alternate therapy: Ibandronate, raloxifene, teriparatide Reassess at least yearly for response to therapy and fracture risk Increasing or stable BMD and no fractures, T score better than -2.5 Progression of bone loss or recurrent fractures Consider a bisphosphonate holiday in 3-5 years Assess compliance, re-evaluate for causes of secondary osteoporosis and factors leading to suboptimal response to therapy Resume therapy when a fracture occurs, BMD declines beyond LSC, or patient meets initial treatment criteria Switch to injectable antiresorptive if on oral agent; switch to teriparatide if on injectable antiresorptive or at very high risk of fracture 18

19 Continued from page 1 Prior fragility fractures or indicators of higher fracture risk Teriparatide, denosumab, zoledronic acid Alternate therapy: Alendronate, risedronate, ibandronate, raloxifene Reassess at least yearly for response to therapy and fracture risk Teriparatide for up to 2 years Denosumab and zoledronic acid Sequential therapy with oral or injectable antiresorptive agent Continue therapy or switch to teriparatide if with progression of bone loss or recurrent fractures *10 year major osteoporotic fracture 20% and hip fracture risk 3% or above country specific threshold **Indicators of higher fracture risk: advanced age, frailty, prior fractures, glucocorticoids, very low T-scores. See table When Should Patients Be Referred to Clinical Endocrinologists? R37. When a patient with normal BMD sustains a fracture without major trauma R38. When recurrent fractures or continued bone loss occurs in a patient receiving therapy without obvious treatable causes of bone loss R39. When osteoporosis is unexpectedly severe or has unusual features R40. When a patient has a condition that complicates management (for example: renal failure, hyperparathyroidism, malabsorption) 19

20 Additional Questions 20