OSTEOPOROSIS BREAKING AWAY FROM BONE LOSS

Transcription

1 OSTEOPOROSIS BREAKING AWAY FROM BONE LOSS CAITLIN SCHMITT, DO COX FAMILY MEDICINE RESIDENCY PGY2 JUNE 26, 2017 Qestion 1 All of the following are risk factors for osteoporosis EXCEPT: A. Low calcim intake B. Smoking C. Alcohol se D. Trner s Syndrome E. Obesity* Qestion 2 Which of the following medical conditions or medications can lead to secondary osteoporosis? A. Hypothyroidism B. Zinc deficiency C. Anticonvlsants (i.e. phenytoin)* D. ACE inhibitors

2 Qestion 3 A 65-year-old Cacasian lady presents to clinic to discss the reslts of BMD testing. Her personal medical history is nremarkable. Her mother, however, died at age 75 de to complications with hip fractre. Her T-score is Which of the following choices is the correct interpretation of her BMD and treatment? A. Normal BMD; calcim spplementation B. Osteopenia; zinc spplementation for prevention C. Osteopenia; alendronate for treatment* D. Osteoporosis; risedronate for treatment Qestion 4 Mrs. S is a 68-year-old Cacasian woman who has been treated with alendronate 70 mg/week for osteoporosis for 2 years. She is otherwise healthy with no previos history of fractres. She has a healthy BMI with a healthy diet and exercises 4x/ week, is a non-smoker, and has only the occasional glass of wine with dinner. A recent DEXA revealed that T-score of her lmbar spine is -2.8 and of her hip is This is 5% lower at the spine and 3% lower at the hip compared to her previos testing. Why did her bone density decrease? Qestion 4 Which of the below cold have cased her BMD to decrease? A. Mrs. S lost BMD despite a prescription of effective treatment. B. Measrement imprecision. C. Mrs. S is compliant with her bisphosphonate, bt does not reglarly take calcim and vitamin D. D. Secondary cases of osteoporosis. E. All of the above. *

3 Qestion 5 Ms. B is a 72-year-old lady who has been on an oral bisphosphonate for 7 years. Her femoral neck T-score is crrently -2.2 and she has had a minimal decline of BMD of 1.5% dring dration of therapy. She is compliant with this medication as well as calcim and vitamin D. She has no history of previos fractres, no family history of osteoporosis, and workp for secondary cases is negative. Her FRAX score for major osteoporotic fractre is 12% and for hip fractre is 2.7% What shold she do now? Qestion 5 What shold Ms. B do now? A. Contine bisphosphonate. B. Take a bisphosphonate holiday.* C. Switch medications. Objectives 1. Define and nderstand the basic pathophysiology of osteoporosis 2. Gain an nderstanding of risk factors and risk assessment for osteoporosis 3. Determine who shold be screened for osteoporosis and associated diagnostic criteria 4. Evalate crrent treatment recommendations for osteoporosis, both pharmacologic and non-pharmacologic 5. Assess monitoring parameters and dration of therapy for varios pharmacologic agents 6. Review means of preventing osteoporosis in mltiple poplations.

4 Definition National Osteoporosis Fondation: A chronic, progressive disease characterized by low bone mass, microarchitectre deterioration of bone tisses, bone fragility, and a conseqent increase in fractre risk Definition Pathogenesis Osteoclasts degrade bone matrix faster than osteoblasts rebild it Inadeqate peak bone mass Excessive bone resorption Inadeqate formation of new bone dring remodeling Maximm bone mineral density (BMD) is achieved by 40 years old as measred by DEXA Peak period of bone mass accral between 11 and 14 years old Varies by gender, ethnicity, body size, region of bone Silent disease Osteoclasts Osteoblasts Osteoclasts Osteoblasts

5 Pathogenesis Epidemiology 10.2 Americans with osteoporosis and 43.4 million with low bone mass 9 million osteoporotic fractres worldwide (2000) 2 million in US, >70% women ~50% of white women and ~20% of white men have osteoporosis-related fractre in their lifetime Hip fractre: mortality rate 5 years 20% greater than expected <1 in 4 women >67 years old ndergo testing or begin treatment Annal healthcare costs (2002) 500,000 hospitalizations 800,000 emergency department visits 2.5 million office visits 180,000 nrsing home admissions Projected total costs of $25 billion in 2025 Organizations National Osteoporosis Fondation American Association of Clinical Endocrinologists American College of Rhematology US Preventive Services Task Force American Academy of Family Physicians American College of Obstetrics and Gynecology International Society for Clinical Densitometry North American Menopase Society

6 Risk Factors Excessive alcohol intake Men: >4 drinks per day; Women: >2 drinks per day Excessive caffeine intake >2.5 cps coffee per day, >5 cps tea per day Tobacco se Family history of osteoporotic fractre Immobilization and inadeqate activity Low body weight <58 kg/128 lb Increasing age Low calcim or vitamin D intake Personal history of fractre White or Asian race Risk Assessment Fractre Risk Assessment Tool (FRAX) Lanched in 2008 by the University of Sheffield Predicts 10-year probability of fractre based on risk factors with or withot BMD Major osteoporotic fractre and hip fractre Risk Assessment FRAX

7 Risk Assessment FRAX Risk Assessment FRAX Risk Assessment FRAX

8 Risk Assessment FRAX Risk Assessment FRAX Clinical Presentation No symptoms ntil fractre occrs Most common: vertebral fractre 2/3 are asymptomatic and diagnosed as incidental radiograph findings Hip fractre Risk increases with age By age 80, 15% women and 5% men Colles/distal radis fractre More common in women shortly after menopase Height loss >1.5 in (4 cm)

9 Who to Screen Organization American Association of Clinical Endocrinologists (AACE) Recommendation All women > age 65 All postmenopasal women with: History of fragility fractre after age Osteopenia on radiographs Starting or crrent glcocorticoid therapy 3 months Increased risk of secondary osteoporosis Perimenopasal or postmenopasal women with risk factors if willing to consider pharmacologic intervention: Crrent smoker Early menopase Family history of osteoporotic fractre Excessive alcohol consmption Low body weight History of glcocorticoid therapy 3 months Who to Screen Organization National Osteoporosis Fondation Recommendation All women > age 65 All men > age 70 Postmenopasal women and men age with risk factors Perform BMD with vertebral imaging in those with fractre Vertebral imaging: Women > age 65 and men > age 70 with T-score -1.5 Women > age 70 and men > age 80 regardless of T-score Postmenopasal women and men > age 50 with fragility fractre Postmenopasal women and men age with height loss 4cm, or recent or ongoing long-term glcocorticoids To check for secondary osteoporosis Who to Screen Organization American College of Obstetricians and Gynecologist (ACOG) U.S. Preventive Services Task Force (USPSTF) Recommendation All women > age 65 No more than once every two years nless new health risks develop Selective screening in women < age 65 If postmenopasal and have osteoporosis risk factors or fractre In absence of new risk factors, do not repeat DEXA if BMD stable or improved Women > age 65 Yonger women whose fractre risk is 65 year old white woman who has no additional risk factors Insfficient evidence for screening in men

10 Diagnosis Dal Energy X-ray Absorptiometry (DEXA) T-score: SD difference between patient s BMD and yong adlt reference poplation Z-score: SD difference between patient s BMD and age-matched poplation Used in premenopasal women Peripheral testing pdexa Qantitative ltrasond (QUS) Peripheral qantitative compted tomography (pqct) Diagnosis WHO Diagnostic Criteria Category Bone Mass (from DEXA) Normal T-score -1.0 Osteopenia (low bone mass) T-score < -1.0 and > -2.5 Osteoporosis T-score -2.5 Severe osteoporosis T-score -2.5 pls one or more fragility fractres Diagnosis T-scores only apply to postmenopasal women and men 50 years old In premenopasal women and men <50 years old, se Z-scores instead Z-score < -2.0 considered abnormal

11 Additional Evalation Most Common 25-OH vitamin D CMP Creatinine Calcim Alkaline phosphatase TSH Consider in selected patients Testosterone in men PTH 24-hor rine cortisol 24-hor rine calcim Secondary Cases COPD Endocrine disorders Primary hyperparathyroidism, hyperthyroidism, Cshing syndrome, primary or secondary hypogonadism, prematre menopase, type 1 diabetes GI disorders Celiac disease, gastric bypass, IBD Hematologic disorders Thalessemia, mltiple myeloma, lekemia Severe liver disease Renal failre Ntrition disorders Anorexia nervosa, malntrition, alcoholism, vitamin D deficiency Rhematoid arthritis Medications Anticonvlsants, chemotherapetics, cyclosporine, Depo-Provera, glcocorticoids, GnRH agonists and antagonists, heparin, lithim, PPIs, SSRIs Treatment Non-pharmacologic Alcohol moderation Men: 4 drinks per day; Women: 2 drinks per day Decreased caffeine intake 2.5 cps coffee per day, 5 cps tea per day Exercise Minimm: 30 mintes 3x/week Resistance training, jogging, walking, balance training Falls risk assessment and edcation Hip protectors Physical therapy Smoking cessation Snlight Calcim and vitamin D spplementation 1200 mg calcim and 800 IU vitamin D per day

12 Treatment Pharmacologic Goal of treatment: fractre prevention Bisphosphonates: first line Alendronate (po) Ibandronate (po and IV) Risedronate (po) Zoledronic acid (IV) Hman monoclonal antibody Denosmab (sbq) Recombinant parathyroid hormone Teriparatide (sbq) SERM Raloxifene (po) Treatment Treatment Bisphosphonates

13 Treatment Bisphosphonates Mechanism: inhibit osteoclast activity, antiresorptive Alendronate and risedronate Dose: Alendronate: 70 mg po once weekly Risedronate: 150 mg po once monthly Redction in risk of hip and vertebral fractres Decrease vertebral fractres in men and glcocorticoid-indced osteoporosis Ibandronate Dose: 150 mg po once monthly or 3 mg IV every 3 months Redction in risk of vertebral fractres only Zoledronic acid Dose: 5mg IV once per year Redces hip and vertebral fractres Treatment Bisphosphonates Contraindications Inability to follow dosing reqirements (po) Esophageal disorders (po) CKD with GFR <30 ml/min Bariatric srgeries with srgical anastomoses (Rox-en-Y) Adverse Reactions GI: reflx, esophagitis, esophageal lcers (po) Fl-like symptoms (IV) Hypocalcemia Renal impairment Less common: mscloskeletal pain, atrial fibrillation, oclar side effects, osteonecrosis of the jaw, atypical femr fractres Treatment Denosmab

14 Treatment Denosmab Mechanism: inhibits osteoclast formation and activity by blocking receptor activator of nclear factor kappa-b ligand (RANKL) Dose: 60 mg sbq every 6 months Decreases risk of hip, vertebral, and non-vertebral fractres compared to calcim and vitamin D spplementation Significantly increases BMD compared to alendronate Adverse reactions Hypocalcemia Back, extremity, and mscloskeletal pain Hypercholesterolemia Cystitis Eczema Treatment Teriparatide Treatment Teriparatide Mechanism: increases bone anabolic activity Candidates Women with severe bone loss (T-score <-3.5 or T-score -2.5 with fragility fractre) Men with osteoporosis and high fractre risk Failed bisphosphonate therapy Dose: 20 mcg sbq once daily Decreases risk of vertebral and nonvertebral fractres Follow with bisphosphonate therapy

15 Treatment Teriparatide Contraindications Primary or secondary hyperparathyroidism Hypercalcemic disorders Increased risk for osteosarcoma History of radiation Unexplained elevated alkaline phosphatase Adverse reactions Hypercalcemia Hypercalciria Hypotension, tachycardia Osteosarcoma Treatment SERMs Treatment SERMs (raloxifene) Mechanism: binds to estrogen receptor and is estrogen agonist to bone, inhibiting bone resorption Candidates: postmenopasal women with osteoporosis who cannot tolerate bisphosphonates, have no history of VTE, and are high-risk for breast cancer Decreases risk of vertebral fractres only Decreased risk of invasive breast cancer Contraindications: history of VTE, PE Adverse reactions Increased vasomotor symptoms Increased risk of VTE Stroke

16 Treatment Other Hormone therapy: estrogen with or withot progesterone However, risks otweigh benefits Risks of se: VTE, stroke, CAD, breast cancer Calcitonin: nasal spray with antiresporptive properties Decreases vertebral fractres only Modest analgesic effect in acte and chronic vertebral fractre Less effective, therefore not first line Increased cancer rate? Combination therapy: stdies ongoing, bt no effectiveness demonstrated Treatment Monitoring Ideally, complete DEXA at same facility sing same machine and technologist with same regions of interest Repeat DEXA every 1-2 years or a less-freqent interval depending on clinical circmstance Consider monitoring bone tmor markers (BTMs) Assesses compliance and efficacy Antiresorptive therapy: expect redction in BTMs Anabolic therapy: expect increase in BTMs

17 Monitoring Sccessfl treatment No new fractres Stable or increasing BMD Antiresorptive agents: BTMs at or below median vale for premenopasal women Consider alternative therapy or reassessment for secondary cases with recrrent fractres or significant bone loss Dration of Therapy Bisphosphanates: consider holiday Teriparatide: 2 years Denosmab and raloxifene: as long as clinically appropriate Dration of Therapy Bisphosphonate holiday Medication accmlates and may have prolonged residence time in bone, therefore residal therapetic effect after stopping High-risk patients Oral: treatment dration of 10 years Zoledronic acid: treatment dration of 6 years Consider teriparatide or raloxifene dring holiday Low-risk patients Oral: consider drg holiday after 5 years of stability Zoledronic acid: consider drg holiday after 3 years of stability Contine to monitor to determine when holiday shold end

18 Up and Coming PTH analog: abaloparatide Hman monoclonal antibody: romosozmab, blosozmab Cathepsin K inhibitor: odanacatrib Prevention Calcim Women age 50, men age 70: 1,000 mg daily Women > age 50, men > age 70: 1,200 mg daily Dairy prodcts, greens, fortified foods Vitamin D < age 50: IU age 50: 800-1,000 IU Snlight, wild-caght tna and salmon, fortified foods USPSTF: vitamin D spplementation is effective in preventing falls in commnitydwelling adlts > age 65 who are at increased risk of falls Prevention Weight-bearing exercises High-impact: dancing, hiking, jogging, stair climbing, tennis Low-impact: elliptical training, stair-step machines, walking Strengthening exercises Weightlifting (machine or free weight) Elastic bands Body weight exercises

19 Prevention Children and Adolescents In addition to school physical edcation Additional increase of BMD: 4% at spine, 2% at proximal femr Freqency: 3x/week Intensity: high-impact Time: 30 mintes after school Type: 1. Aerobic workots: aerobics, soccer, skipping, ball games, weight training 2. Circit training: 20-minte weight-bearing, strength-bilding circit 1 minte per station 1 set of 10 repetitions progressing to 3 sets of 10 over time Prevention Yong Adlts and Pre-Menopasal Women Exercise may decrease vertebral fractre risk in addition to increase BMD BMD increase: 2% at spine and femoral neck Freqency: 3x/week Activity Warm-p High-impact jmps Stretching and non-impact activities Cool-down 15 mintes 20 mintes 15 mintes 10 mintes Dration Prevention Yong Adlts and Pre-Menopasal Women BMD increase: 5% at spine and 3% at femoral neck Freqency: 3x/week Class 1: Every 12 mintes, alternate between exercise stations and high-impact aerobic activities Exercise stations: psh-ps, sit-ps, arm crls, barbell presses Class 2: Moderate weights to exercise gltes maxims, erector spinae, sholder girdle mscles Class 3: Vigoros, high-impact aerobic workot with HR between 70-85% max

20 Prevention Postmenopasal women Freqency: 4x/week with two grop minte sessions and two at-home 25 minte sessions Warm p/endrance seqence: walking to rnning 20 mintes Jmping seqence: rope-skipping, closed-leg jmps Strength-training seqence: resistance machines and isometric exercises Flexibility-training Prevention Best Bones Forever! Prevention U.S. Bone and Joint Initiative PB&J: Protect Yor Bones & Joints Fit to a T

21 Conclsions Osteoporosis-related fractres case decreased qality of life, increased mortality, and significant healthcare costs. Screening for osteoporosis is based on age, increased fractre risk, and secondary cases. DEXA is the gold standard for screening and diagnosis, sing T-scores in postmenopasal women and men over age 50 and Z-scores in premenopasal women and men yonger than 50. Bisphosphonates are first line treatment, bt denosmab, teriparatide, and raloxifene are additional effective options. Lifestyle modification shold be discssed with patients of all ages to prevent and treat osteoporosis. Qestion 1 All of the following are risk factors for osteoporosis EXCEPT: A. Low calcim intake B. Smoking C. Alcohol se D. Trner s Syndrome E. Obesity* Qestion 2 Which of the following medical conditions or medications can lead to secondary osteoporosis? A. Hypothyroidism B. Zinc deficiency C. Anticonvlsants (i.e. phenytoin)* D. ACE inhibitors

22 Qestion 3 A 65-year-old Cacasian lady presents to clinic to discss the reslts of BMD testing. Her personal medical history is nremarkable. Her mother, however, died at age 75 de to complications with hip fractre. Her T-score is Which of the following choices is the correct interpretation of her BMD and treatment? A. Normal BMD; calcim spplementation B. Osteopenia; zinc spplementation for prevention C. Osteopenia; alendronate for treatment* D. Osteoporosis; risedronate for treatment Qestion 4 Mrs. S is a 68-year-old Cacasian woman who has been treated with alendronate 70 mg/week for osteoporosis for 2 years. She is otherwise healthy with no previos history of fractres. She has a healthy BMI with a healthy diet and exercises 4x/ week, is a non-smoker, and has only the occasional glass of wine with dinner. A recent DEXA revealed that T-score of her lmbar spine is -2.8 and of her hip is This is 5% lower at the spine and 3% lower at the hip compared to her previos testing. Why did her bone density decrease? Qestion 4 Which of the below cold have cased her BMD to decrease? A. Mrs. S lost BMD despite a prescription of effective treatment. B. Measrement imprecision. C. Mrs. S is compliant with her bisphosphonate, bt does not reglarly take calcim and vitamin D. D. Secondary cases of osteoporosis. E. All of the above. *

23 Qestion 5 Ms. B is a 72-year-old lady who has been on an oral bisphosphonate for 7 years. Her femoral neck T-score is crrently -2.2 and she has had a minimal decline of BMD of 1.5% dring dration of therapy. She is compliant with this medication as well as calcim and vitamin D. She has no history of previos fractres, no family history of osteoporosis, and workp for secondary cases is negative. Her FRAX score for major osteoporotic fractre is 12% and for hip fractre is 2.7% What shold she do now? Qestion 5 What shold Ms. B do now? A. Contine bisphosphonate. B. Take a bisphosphonate holiday.* C. Switch medications. Key References The American Association of Clinical Edocrinologists, The Voice of Clinical Endocrinology Fonded in The American Association of Endocrinologists. Calcim/Vitamin D. National Osteoporosis Fondation. Exercise Recommendations. International Osteoporosis Fondation. FRAX Calclation Tool. The University of Sheffield. Jeremiah, Michael P et al. Diagnosis and Management of Osteoporosis. Diagnosis and Management of Osteoporosis American Family Physician. 15 Ag NOF BoneSorce MyNOF. Official Positions International Society for Clinical Densitometry (ISCD). International Society for Clinical Densitometry ISCD Official Positions Comments.

24 Qestions? Thank yo! Caitlin Schmitt, DO Cox Family Medicine Residency PGY2