Sarena Ravi MD, MPH Endocrinologist. Franciscan Physicians Network Division of Endocrinology Chicago, IL

Transcription

1 Sarena Ravi MD, MPH Endocrinologist Franciscan Physicians Network Division of Endocrinology Chicago, IL

2 Definition & Diagnosis of Osteoporosis Management of Osteoporosis in all Populations Long term Management of Osteoporosis

3 Characterized by low bone mass Micro-architectural Disruption Increased Skeletal Fragility Influenced and affected by bone mineral density rates of bone resorption and formation (turnover) bone geometry (size and shape of bone) microarchitecture

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6 Cortical and Trabecular Bone Cortical Bone 80% of all the bone in the body 20% of Bone Turnover Trabecular Bone 20% of all bone in the body 80% of Bone Turnover

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8 T-score <= -2.5 SD s at any site based upon BMD measurement by dual-energy x-ray absorptiometry (DXA) Fragility Fracture! Particularly at the spine, hip, wrist, humerus, rib, and pelvis Commonly missed FRAGILITY fracture means Osteoporosis BMD assessment by DXA does not apply in presence of fragility fracture

9 A T-score that is 1 to 2.5 SD below the young adult mean is termed low bone mass (osteopenia) Normal bone density is defined as a value within 1 SD of the mean value in the young adult reference population There are actually more fractures in patients with a T-score between - 1 and -2.5 because there are so many more patients in this category

10 Bone Fractures which occur spontaneously or from minor trauma Spine, hip, wrist, humerus, rib, and pelvis Clinical diagnosis of Osteoporosis can be made without BMD Fragility fracture result from mechanical forces that would not ordinarily result in fracture: Fall from a standing height or less Bending, vacuuming, picking up something, coughing and sneezing, walking, daily chores, ect Unknown fracture is incidentally found on imaging

11 57 year old, post-menopausal female Referred to me for thyroid lab abnormality autoimmune hyperthyroidism During Chart Review saw imaging fro 2012 reported vertebral compression fracture DXA scan T-scores were not <= -2.5 (did not report osteoporosis) Was told probably early stages of osteoporosis and did not initiate treatment or refer to specialist Patient herself recalls feeling sudden pain in her back that year while vacuuming (no trauma) Is this Osteoporosis? YES!! In setting of fragility fracture BMD/T-score does not apply! Should this be treated? YES!! Initiated treatment with IV Zolendronic Acid

12 Reference population in which the T-score -2.5 SDs below the mean were standardized to were young, Caucasian females Currently extrapolated to older Men > age 50 Above definition of osteoporosis based on population of Caucasian Females WHO does not have enough data to create definitions for Men or other Ethnic Groups Even in setting of fragility fracture DXA may not be able to report osteoporosis Above Criteria cannot be used in Pre-menopausal women and Men <50 Cannot be used in children

13 WHO: all cut-off values are somewhat arbitrary, but a measured value of bone mineral more than 2.5 standard deviations below the mean for young healthy women at any site (spine, hip, mid-radius) identifies 30 % of all postmenopausal women as having osteoporosis, more than half of whom will have sustained a prior fracture of the proximal femur, spine, distal forearm, proximal humerus or pelvis. Other reasons DXA findings not always accurate: Positioning and errors by technician Variability in machine same machine should be used each time Errors in demographic reporting (age, ect ) Wrong scan mode, invalid skeletal site, inability to report LSC, artifacts, arthritis, ect

14 T-Score WHO Criteria should NOT be applied to Pre-Menopausal women or Men <50 Relationship between BMD and fracture risk is not the same in younger women/men Z-Score Comparison of the patients BMD to an age-matched population -2 or below is considered below expected range for age Coexisting problems should be investigated such as alcoholism and steroid therapy Applied in Children, Men <50, and Pre-Menopausal women

15 Who should be screened for Osteoporosis? National Osteoporosis Foundation (NOF): Women >65 and Men >70 (regardless of clinical RF) Younger Postmenopausal women, women in menopausal transition, and men age with clinical risk factors Adults with fragility fracture >50 years Adults with underlying chronic conditions (eg RA), chronic glucocorticoid use, or other pharmaceutical therapies associated with low BMD AACE Similar to NOF Any adult with a fragility fracture No recommended guidelines for men

16 Clinical Risk Factors & Secondary Causes of Osteoporosis that support early screening: (Women <65, Pre-menopausal, Men 50-69, Men <50) Drugs: Glucocorticoids, Immunosuppressants, Anti-seizure, GnRH agonists/antagonists, Heparin, Chemotherapy GI/Nutrition: Liver disease, Chronic cholestasis, Gastrectomy/GI Surgeries, Malabsorption, Pancreatic disorder, Vit D/Ca deficiency Endocrine: Cushing s, Acromegaly, Adrenal Insufficiency, Eating Disorders, Hyperparathyroidism, Hyperthyroidism, Hyperprolactinemia, Hypogonadism, DM

17 Clinical Risk Factors & Secondary Causes of Osteoporosis that support early screening: (Women <65, Pre-menopausal, Men 50-69, Men <50) Marrow Related Disorders: Hemochromatosis, Multiple Myeloma, Sarcoidosis, SSA/Thalassemia, Lymphoma, ect Organ Transplantation Misc/Genetic: Hemophilia, Idiopathic Hypercalciuria, Ankylosing spondylitis, MS, RA, OI

18 Who should be treated? Management Varies: Post-Menopausal Females and Men > 50 T-score and BMD used to guide treatment/management WHO criteria on T-score should be used Pre-Menopausal Females and Men < 50 WHO criteria on T-score should NOT be used Relationship between BMD and fracture not the same in younger men/women Z-Scores (esp children)

19 Lifestyle measurements & Fall precautions Smoking, Alcohol, Exercise, Diet, Hip Protectors Calcium + Vitamin D Pharmacological Therapy: Bisphosphonates: Anti-resorptive therapy Reduce activity of bone-resorbing Osteoclasts Alendronate, Ibandronate, Risedronate, and Zoledronic Acid Denosumab: Anti-resorptive therapy Decreases formation, differentiation, of Osteoclasts and decreases function of active Osteoclasts Raloxifene Teriparatide/Abaloparatide Anabolic agent

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26 T-Score <= -2.5 at any site (AACE) Total hip, Femoral Neck, Lumbar Spine, 33% (1/3 rd ) or Radius Even in the absence of prevalent fracture Osteopenia (T-Score between -1.0 and -2.5) if Fracture Risk is High! Chronic Glucocorticoid Use High Frax Score Fragility Fracture!! Regardless of T-score

27 Osteopenia with high FRAX Score Treat same way as osteoporosis! FRAX Score 10-year probability for Major osteoporotic fracture and Hip fracture >= 20% for Major Treatment with pharmacologic therapy >= 3% for Hip Treatment with pharmacologic therapy Age, height, weight, family history, parent with hip fx, prior fracture, smoking, alcohol use, secondary causes, RA, steroid use, ethnicity, BMD at femoral neck, type of DXA machine All these factors used to calculate FRAX Score Calculation tool where we enter the date score is then given Does not apply when T-score <= -2.5 or if Fragility Fracture Already Osteoporosis! Does not apply to patients already being treated for Osteoporosis

28 Indicate patient s RISK for Fracture Low Mild Moderate High Management Varies LOW Risk Osteopenia No pharmacological treatment Lifestyle measures, Ca, Vitamin D, Fall Precaution

29 MILD Risk Pharmacological Therapy Osteopenia with high FRAX Score/High Fracture Risk Initiate with Bisphosphonates (if no C/I) Treat for 3-5 years (IV/PO) DXA/BMD every 1-2 years Increasing or stable Initiate Drug Holiday End Drug Holiday and Re-Initiate Pharmacological Therapy if: Fragility Fracture Significant Decline in BMD based LSC

30 Moderate Fracture Risk Osteoporosis Per WHO Criteria for T-score No Prior Fragility Fracture, No chronic steroid therapy, T-score not severely low Pharmacological Therapy Bisphosphonates or Denosumab DXA every 1-2 years Increasing or stable BMD Drug Holiday Resume Therapy If: Fragility fracture Significant Decline in BMD Bone Turnover Markers rise to pre-treatment levels Resume therapy 3-5 years after drug holiday

31 Moderate Fracture Risk Osteoporosis Per WHO Criteria for T-score No Prior Fragility Fracture, No chronic steroid therapy, T-score not severely low Pharmacological Therapy Bisphosphonates or Denosumab DXA every 1-2 years Decrease in BMD or Fragility Fracture Assess Compliance Re-evaluate for Secondary Causes! Switch to Injectable if on PO Switch to Anabolic agent (Teriparatide) if on Injectable

32 High Fracture Risk Prior Fragility Fracture Advanced Age, Frailty, Glucocorticoids, Very Low T-Scores, Fall Risk Pharmacological Therapy Teriparatide/Abaloparatide, Denosumab, Zoledronic Acid DXA /BMD yearly or every 1-2 years Denosumab Continue therapy (Drug holiday?) Significant Decline in BMD Teriparatide or anabolic agent Teriparatide (Anabolic) - Only up to 2 years max Sequential Therapy with oral/iv antiresorptive agent! BMD begins to decline after ending therapy Zoledronic Acid Continue for 6 years Significant Decline in BMD Anabolic Agent (Teriparatide)

33 Lifestyle changes (diet, smoking, alcohol, ect ) Calcium + Vitamin D (adequate dietary and supplemental intake) FDA Approved Therapy: Alendronate, Risedronate, Zoledronic Acid Hip Fracture Zoledronic Acid Ibandronate not approved Teriparatide (Abaloparatide only for post-menopausal females) Denosumab only for men receiving ADT for prostate cancer Not YET been shown to prevent fracture in other men Used in clinical practice still does have beneficial effect on BMD Intolerant to other therapies or Impaired Renal Function

34 HYPOGONADISM and OSTEOPOROSIS For men at high risk of fracture and on testosterone therapy Add agent with proven anti-fracture efficacy (e.g. a bisphosphonate or teriparatide). Men at borderline/moderate high risk for fracture with hypogonadism Testosterone therapy in lieu of a bone drug After 2 years of testosterone therapy BMD T-score <-2.5 Add Established Osteoporosis therapy If Testosterone therapy contraindicated Osteoporosis therapy Contraindications to all approved Osteoporosis therapy Suggest testosterone therapy for men at high risk for fracture If established hypogonadism

35 Secondary Causes!! BMD/DXA Testing in these populations if: History of Fragility Fracture Diseases, conditions, or medications associated with low bone mass/bone loss Considering pharmacologic therapy for osteoporosis Monitoring Drug Therapy for Osteoporosis Women in Menopausal Transition if RF are present Low body weight, prior low-trauma fracture, high risk medications, ect

36 Secondary Causes!! Management Ca + Vitamin D (diet + supplements) Weight Bearing Exercises/Lifestyle changes (smoking, alcohol, nutrition ) Treatment of Secondary Causes! Not the same as post-menopausal or men > 50 Pharmacologic Treatment in Selected Cases Refer to Specialist!! Endocrine, Rheumatology, University Center, Specialized Bone Center, ect

37 Table 11 Causes of Secondary Osteoporosis in Adults Endocrine or metabolic causes Nutritional/GI conditions Drugs Disorders of collagen metabolism Other Acromegaly Diabetes mellitus Type 1 Type 2 Growth hormone deficiency Hypercortisolism Hyperparathyroidism Hyperthyroidism Hypogonadism Hypophosphatasia Porphyria Pregnancy Alcoholism Anorexia nervosa Calcium deficiency Chronic liver disease Malabsorption syndromes/ malnutrition (including celiac disease, cystic fibrosis, Crohn s disease, and gastric resection or bypass) Total parenteral nutrition Vitamin D deficiency Antiepileptic drugsa Aromatase inhibitors Chemotherapy/ immunosuppressants Depo-Provera Glucocorticoids Gonadotropin-releasing hormone agents Heparin Lithium Proton pump inhibitors Selective serotonin reuptake inhibitors Thiazolidinediones Thyroid hormone (in supraphysiologic doses) Ehlers-Danlos syndrome Homocystinuria due to cystathionine deficiency Marfan syndrome Osteogenesis imperfect AIDS/HIV AS COPD Gaucher disease Hemophilia Hypercalciuria Immobilization Major depression Myeloma and some cancers Organ transplantation Renal insufficiency/ failure Renal tubular acidosis Rheumatoid arthritis Systemic mastocytosis Thalassemia

38 All Populations with Osteoporosis/Low BMD: CBC/CMP/Phos PTH TSH Vitamin D levels Celiac SPEP/UPEP Test for Cushing s If Clinically Suspicious 24 Hr Urinary Calcium Suspicion of malabsorption, Kidney stones, PTH disorder, Bariatric/GI surgeries More Extensive Testing/Secondary Workup: Pre-Menopausal Females and Men <50 Post-Menopause and Men >50 If Suspicious Clinical Features Present

39 Ca + Vitamin D Supplementation or Adequate Dietary Intake Men > 50 and Post-Menopausal Females Treat if Osteoporosis Present Any dose or duration of GC Men > 50 and Post-Menopausal Females Osteopenia and High risk Treat with Pharmacological Therapy Any dose or duration of GC Therapy All Other Men > 50 and Post-Menopausal Females Prednisone >= 7.5 mg/day or Equivalent for greater than 3 months Treat with Pharmacological Therapy For Prevention Men < 50 and Pre-Menopausal Females Hypogonadism, Fragility Fracture, Z-Scores, Accelerated Bone Loss on DXA Individualized to Patient Refer Specialist

40 Refer to Endocrinology, Rheumatology, University Bone Clinic Pre-menopausal females & Men < 50 Management is Different! Secondary Causes MUST be Investigated and Treated Pediatric Population and Very Young Men/Women Post-Menopausal Women and Men > 50 Chronic management requires experience reading DXA images, BMD comparisons using LSC, Knowledge on Contraindications and SE of Osteoporosis Therapy Chronic management by same provider(s) crucial for appropriate long term care May not have access to prior DXA s for comparisons Patients may not know prior treatments or remember where they were treated Also may now know what years and duration they were treated for osteo Decisions on terminating or continuing Drug Holidays will be difficult

41 Osteoporosis and Chronic Kidney Disease (CKD) Risk for CKD-MBD (Mineral Bone Disease) Renal Osteodystrophy: Adynamic Bone Disease & Osteomalacia Underproduction of Bone Cannot treat with Osteoporosis Therapy Bisphosphonates not recommended in GFR < 35 Specialized Bone Centers may still administer them Anabolic Agents (Forteo & Tymlos) Must be used with caution Risk of 2ndary Hyper-PTH in CKD Denusomab can possibly used in GFR < 30 Not recommended due to risk of Hypocalcemia Very Close Monitoring Underproduction of Bone Cannot treat with Osteoporosis Therapy All cases should have close monitoring by multiple specialists including Nephrology

42 When taking history from New Patients I took Fosamax for 1-2 years was told to stop because it wasn t working I took Fosamax for 12 years I believe I ve been on Fosamax, and Boniva for a few years, and also Actonel I m not sure when my last DXA scan was, or where I had it, or who my doctor was at the time

43 I had a compression fracture, DXA was normal so was never treated I took Fosamax from in my late 30 s early 40 s I ve been on Prolia for few years no never seen Nephrology (Female pt with GFR in the 30 s) I ve been on Fosamax for more than 5 years, I was told to continue it GFR declined to 20 s (Diabetic Nephropathy)

44 When taking history from New Patients I took Fosamax for 1-2 years was told to stop because it wasn t working I took Fosamax for 12 years All Bisphosphonates and Denosumab have a recommended length of treatment before a Drug Holiday Improvements should be assessed over a 3-10 year period not just 1-2 years I believe I ve been on Fosamax, and Boniva for a few years, and also Actonel Makes it difficult to decide on terminating or continuing a Drug Holiday I m not sure when my last DXA scan was, or where I had it, or who my doctor was at the time Without prior DXA/BMD, cannot compare to recent numbers Stability vs. Significant Changes in BMD helps determine further management

45 When taking history from New Patients I had a vertebral fracture DXA was normal so was never treated First Case: Fragility fracture Osteoporosis!! I took Fosamax from in my late 30 s early 40 s How was Osteoporosis diagnosed? (Z-score or T-score?) Secondary work up?? I ve been on Prolia for few years no never seen Nephrology Female pt with GFR in the 30 s Risk for Adynamic Bone Disease should be assessed I ve been on Fosamax for several years, I was told to continue it GFR declined to 20 s (Diabetic Nephropathy) Bisphosphonates should not be used GFR < 35

46 Referred to me for uncontrolled IDDM with hypoglycemia in setting of CKD Chart Review: Osteoporosis diagnosed in 2011 (T-score) Never Treated : Multiple (3) Vertebral fractures developed GFR declined from 50 s to 20 s Significant Chronic Back Pain, Severe decline in mobility, Impaired Ambulation with Inability to do Several Daily Activities Compression fractures led to Central Canal compromise with Spinal Cord Compression Transferred to University Hospital for Neurosurgery management Post-Discharge Months of Rehab

47 GFR Decline from 50 s to 20 s in 1 year ( ) Treatment BEFORE Decline in GFR would have been greatly beneficial Untreated Osteoporosis & Overlooking Fragility Fractures Very Debilitating for patient Increased Morbidity Significant Increases in Cost

48 MAJOR POINTS Fragility Fracture Osteoporosis! Long Term Management Contraindications in therapy (eg GFR..) Dx of Osteoporosis Begin Therapy Commonly Overlooked Secondary Work-up Pre-Menopausal Females and Men < 50 More in depth Secondary work up! Osteopenia with High Risk Treat as Osteoporosis! Chronic Glucocorticoids Assess Fracture Risk

49 Clinical Practice Guidelines for the Diagnosis and Treatment of Postmenopausal Osteoporosis - AACE/ACE Postmenopausal Osteoporosis CPG. Camacho, Pauline M et al Endocr Pract. 2016;22(Suppl 4) Osteoporosis in Men: An Endocrine Society Clinical Practice Guideline. Watts, Nelson B et al. The Journal of Clinical Endocrinology & Metabolism, Volume 97, Issue 6, 1 June 2012, Pages American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis. Buckley L, et al. Arthritis Rheumatol. 2017;69(8):1521. Epub 2017 Jun 6. Factors related to variation in premenopausal bone mineral status: a health promotion approach. Tudor-Locke C, McColl RS SO Osteoporos Int. 2000;11(1):1. Epidemiology and clinical features of osteoporosis in young individuals.aukhosla S, Lufkin EG, Hodgson SF, Fitzpatrick LA, Melton LJ 3rd SO Bone. 1994;15(5):551. Low bone mass in premenopausal parous women: identification and the effect of an information and bone density feedback program. AUJones G, Scott F SOJ Clin Densitom. 1999;2(2):109.