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Age-related Bone Loss and Osteoporosis Nahid Rianon, MD, DrPH The University of Texas Health Science Center at Houston Assistant Professor, Division of Geriatric and Palliative Medicine, Department of Internal Medicine Dr. Nahid Rianon was a member of the Houston Geriatric Education Center faculty. During her time with the grant, she developed and presented these slides to an interprofessional audience. Dr. Rianon is with The University of Texas Health Science Center at Houston. She is an Assistant Professor, Division of Geriatric and Palliative Medicine, Department of Internal Medicine. 2 This project was funded by a grant from the Health Resources and Services Administration (HRSA) of the Department of Health and Human Services. The grant was initially funded in 2007 with renewed funding for five years beginning in 2010. (Grant #UB4HP19058). The grant was successfully completed in June, 2015. Attendees will recognize osteoporosis and related fractures as important health care problem of old age Attendees will understand the patho-physiology of age related bone loss Attendees will be able to calculate fracture risk in geriatric patients and treat osteoporosis with an individualized plan for each patient Attendees will be knowledgeable about prevention of age related bone loss & related fractures 5 Rianon- HGEC- Osteoporosis , 2015 Fractures can decrease quality of life: Physical: pain, compressed abdomen, spinal deformity Functional: decreased mobility Psychosocial: depression Rate of recurrent vertebral fracture after the initial one: ~5-20% NOF Hip fracture ~50% with hip fractures will never walk w/o assistance ~25% will require long-term care 6 Rianon- HGEC-Osteoporosis, 2015 ~ $22 billion is spent annually for osteoporosis and related fracture in the Blume & Curtis, 2010 USA ~ $7 billion is spent annually for breast State of Health Care Quality, 2007 cancer in the USA 7 Rianon- HGEC-Osteoporosis, 20145 ~10,000 baby boomers turn 65 everyday Number of elderly Americans (≥65 yrs) 34 million in 1998 to ~ 70 million in 2030 Concerns of under-recognition and under-treatment ~20% f/u for treatment after fragility fractureOwn the Bone Fracture- often first sign of presence of osteoporosis ~ half of the osteoporosis related office visits managed by PCPs 5% in 2002 to 20% in 2008 (NHAMCS)Rianon et al., 2013 HTN, ↑ lipid, OA, DM & depression - common in them Barriers For PCPs/Geriatricians: Competing chronic disease priorities & lack of resources Rapidly growing geriatric population – not enough trained specialty care physicians 8 Rianon- HGEC-Osteoporosis, 2014 Osteoporosis & related fractures - important public health problems of old age ~10 million Americans suffer from osteoporosis NOF ~ 34 million are at risk More than 2 million fractures in the USA in 2005 were attributable to osteoporosis prevalent fractures vertebral fractures (most common) hip fractures wrist fractures 9 Rianon- HGEC-Osteoporosis, 2015 For Women: Incidence of fractures per year exceeds that of stroke, MI & breast cancer combined For Men: Fracture risk is higher than that of prostate cancer ~1 in 2 Caucasian women ≥50 years experience a fracture in their lifetime ~1 in 5 men ≥50 years will experience a fracture Osteoporosis affects men & women of all races/ethnicities 10 Rianon- HGEC-Osteoporosis, 2015 Compromised bone strength that increases risk of fracture Bone Strength is characterized by Bone density & Other bone qualities, e .g., micro-architecture influenced by bone remodeling, bone turnover, mineralization and other factors that are more difficult to quantify, such as “damage accumulation” (NIH consensus conference 2000) 11 Rianon- HGEC-Osteoporosis, 2015 Osteoporotic bone Quantitative & qualitative changes ©2012 Multimedia Scriptorium, UTHealth Trabecular bone Mineral loss Cortical bone Healthy femur Fragility Fractures Loss of mineral & microstructure Rianon- HGEC-Osteoporosis, 2015 mg/cm2 ASBMR 2011 13 Source: ASBMR using data from Looker A et al., 1998 Osteop. Intl Types Trabecular 20% of skeletal mass Greater surface area than cortical Provides supporting strength to the ends of weight-bearing bones Cortical 80% of skeletal mass Solid outside shaft of long bones http://www.asbmr.org/default.aspx Cells Osteoblasts Critical to bone formation Osteoclasts Reabsorb bone Osteocytes Exact role is still under investigationinvolved in bone turnover 14 Rianon- HGEC-Osteoporosis, 2015 Physiology- Normal State Osteoclast Osteoclast Precursor Osteoblast Precursors Osteoblast LEGEND: LC = Lining Cells CL = Cement Line OS = Osteoid BRU = Bone Remodeling Unit Normal Bone Remodeling Sequence Resorption = Formation No change in bone mass Rianon- HGEC-Osteoporosis, 2015 Pathogenesis of age-related bone loss: Unbalanced Remodeling Net bone loss Resorption > Formation Inadequate calcium or vitamin D Menopause Aging Medications or diseases Osteoporosis Normal Bone Structure Osteoporotic Bone Structure Rianon- HGEC-Osteoporosis, 2015 DXA scan - Left hip DXA scan - Lumbar spine Osteoporosis = A T- score of <-2.5 for BMD Osteopenia = A T-score of -1 to -2.5 for BMD Usual sites for DXA are lumbar spine and left hip 17 Rianon- HGEC-Osteoporosis, 2015 Who should we screen: USPSTF 18 Screening: other organizations Organization Recommendations Women men NOF BMD for all ≥65 y & BMD for all ≥70 y postmenopausal <65 y, & 50-69 y, based based on risk profile on risk profile WHO Indirect evidence supports screening for ≥65 y, but no direct evidence for widespread screening ACP ACOG Older men at high risk & candidate for therapy BMD for all ≥65 y & postmenopausal <65 y who have ≥1 risk factor Ann Intern Med. 2011;154:356-364 19 Age (40-90), gender, height & weight, race/ethnicity Previous fracture Rheumatoid arthritis 2ndary Osteoporosis Hip fracture in parents Current smoking Alcohol Glucocorticoids (oral)≥ 3 months @ dose 5mg daily or more – or equivalent doses of other glucocorticoids DM-I, OI in adults, Untreated Hyper or Hypothyroidism, Premature Menopause (<45 yrs), Chronic malnutrition or malabsorption & Chronic liver disease Bone mineral density (BMD) 21 Rianon- HGEC-Osteoporosis, 2015 T-score between -1.0 to Hx of hip fracture 2.5 @ fem. neck, total hip Other prior fractures & or spine AND 2ndary T-score between -1.0 to cause ↑ risk of fracture -2.5 @ fem. neck, total Steroid use, total hip or spine Height loss (vert. frac.)* immobilization, men w/androgen deprivation therapy T-score ≤-2.5 @ fem. neck, total hip or spine T-score between -1.0 to -2.5 @ fem. neck, total hip or spine AND 10-yr probability of hip fracture ≥ 3% or any major osteoporosis-related www.nof.org/professionals/clinical-guidelines fracture ≥ 20% (FRAX) * Hannan et al., 2012 JBMR 22 Rianon- HGEC-Osteoporosis, 2015 Bisphosphonates Oral Alendronate 10 mg daily or 70 mg wkly Risedronate 5 mg daily or 35 mg weekly or 150 mg/mo Ibandronate 150 mg/mo Intra-venous Zoledronic acid 5 mg/yr Teriparatide Recombinant human PTH (not >2 yrs) Contra-indicated in cancer patients) 20 mcg sq daily Denosumab 60 mcg sc/q 6 Humanized monoclonal antibody Calcium (1200-1500 mg) + Vitamin D (800-1000 IU daily) www.nof.org/professionals/clinical-guidelines 23 Rianon- HGEC-Osteoporosis, 2015 SERM Raloxifene – not commonly used because it increases risk of DVT & increased hot flashes Testosterone If hypogonadism is the cause of osteoporosis Caution if history of prostate cancer Estrogen/Progestin Not encouraged due to increased risk of breast cancer, stroke, DVT and coronary diseases www.nof.org/professionals/clinical-guidelines 24 Rianon- HGEC-Osteoporosis, 2015 Calcium 1000-1500 mg daily Consider intake with diet Formulation: Carbonate (with meal) Citrate (fasting state) www.nof.org/professionals/clinical-guidelines; IOM & Endocrine society guidelines Vitamin D Screen at-risk patients Check 25 hydroxy vitamin D total Recommended level 30 ng/dl Ergo/Chole-calciferol 800-1000 IU daily Unless <30 – then 50000 IU q weekly for 8-12 wks 25 Rianon- HGEC-Osteoporosis, 2015 Medication Fracture outcome Side Effects Bisphosphonates Reduces risk of vertebral, non-vertebral & hip (except ibandronate) fracture •Gastro-intestinal irritation •Myalgia & arthralgia •Renal toxicity •Atypical fracture •Osteonecrosis of jaw Teriparatide Reduces risk of both vertebral •Osteosarcoma observed in & non-vertebral fracture rats (contra-indicated in patients with history of cancer) Denosumab Reduces risk of vertebral, non-vertebral & hip fracture Silverman & Christiansen, 2012, Osteop Intl •Dermatitis •Hyporcalcemia •Osteonecrosis of jaw •Pancreatitis 26 Rianon- HGEC-Osteoporosis, 2015 For Bisphosphonates: Alternate options Atypical fracture Switch to other Jaw necrosis agents Severe GERD/gastritis or Teriparatide: up to GI bleed 2 years Unimproved BMD despite treatment Fracture while being on tx Intervention Drug holiday Monitor with DXA/1-2 yrs Monitor bone markers/yr *Rianon N et al., 2011 27 Rianon- HGEC-Osteoporosis, 2015 DXA Acquired BMD Stable or improved BMD Loss of BMD <%CV showing no significant change over mechanical drift from QA report for DXA machine Carey J, 2005; Delmas P et al., 2009; ASBMR Bone Markers Suppression of Bone markers Both formation and resorption markers not a standard practice yet 28 Rianon- HGEC-Osteoporosis, 2015 Fracture Liaison Services (FLS) Goal: Bringing patients back for DXA Improve rates of f/u Results: Improved follow up and prevention Increased continuity and quality of care 29 Rianon- HGEC-Osteoporosis, 2015 ↑case identification,diagnosis,treatmentBogoch et al.,2006, JBJS-Am Increased BMD test (3-45%)Inderjeeth et al., 2010 MJA Liaison between orthopedics & discharge destination health care team (including PCP) ↑ provider awareness & treatmentSwitzer et al.,2009 JortTrau ↑ treatment with documentation & f/uWard et al., 2007 Osteop Int Fracture prevention algorithm Kaiser Permanente, 2009 No information on BTM Inter-professional team worked together 30 Rianon- HGEC-Osteoporosis, 2015 Formation Serum bone specific alkaline phosphatase (BAP) (5.6-29 mcg/L) Serum pro-collagen type 1 aminoterminal propeptide (P1NP) (20-108 mcg/ml) Osteocalcin (8-32 ng/ml) Resorption Serum C-terminal cross-linking telopeptide of type I collages (CTX) Urine N-terminal cross-linking telopeptide of type I collagen (NTX) 2nd void sample in the AM (4-64 nmol BCE/mmol creatinine) ASBMR: http://www.asbmr.org 31 Rianon- HGEC-Osteoporosis, 2015 85 year old CF, BMI 21, lost about 4” since age 30s, no hx of cancer/previous fx/other 2ndary risk of osteop, no FHx of osteop or hip fx in parents, former smoker, social drinker, exercises regularly, hx of tx for osteoporosis w/ bisphosphonates for 14 yrs w/o much improvement in BMD. DXA acquired femur neck T scores since 1997 were: T score Fem Neck Year -2.1 1997 -2.2 2006 -2.1 2008 -2.0 2010 Change from baseline was +2.0% DXA was done using the same machine at the same place U-NTX 18, P1NP 11, Vit D, Calc, PTH, Mg & Phos WNR. What would you do at this point? 32 Rianon- HGEC-Osteoporosis, 2015 • Patient had osteopenia: In a patient with osteopenia – treatment is indicated if FRAX score indicates treatment or she has a history of fragility fracture FRAX not valid for her due to history of treatment with bisphosphonate • Also has a long history (>5 years of bisphosphonate use) • Bone markers are suppressed • Stop bisphosphonate – start drug holiday, monitor in a year • Continue calcium and vitamin D supplementation and weight bearing exercise 33 Rianon- HGEC-Osteoporosis, 2015 http://www.surgeongeneral.gov/library/bonehealth/chapter_6.html#NutritionsImpacto34 nBoneHealthAReviewoftheEvidence Weight bearing exercise Stimulates bone formation 2.5 to 4 hours/wk of moderate to severe intensity physical activity Non-skeletal Environmental/Behavioral Fall prevention Improve balance & gaitPT/OT Smoking cessation Avoid risk level alcohol use Avoid flexion in patients with risk of or hx of Calcium and Vitamin D vertebral fracture Regular supplemental FLS (Fracture Liaison Services) required dose Network within the clinic, or group of providers Chodzko-Zajko WJ et al., 2008 & ASBMR (2ndary prevention) 35 Rianon- HGEC-Osteoporosis, 2015 Osteoporosis is a progressive & chronic metabolic bone disease that decreases bone density with deterioration of bone structure. Clinical Diagnosis = T- score of <-2.5 for BMD Prevention & treatment with a comprehensive and individualized approach. 36 Rianon- HGEC-Osteoporosis, 2015 * Hannan et al., 2012 JBMR Ann Intern Med. 2011;154:356-364 ASBMR: http://www.asbmr.org Bogoch et al.,2006, JBJS-Am Chodzko-Zajko WJ et al., 2008 & ASBMR http://www.asbmr.org/default.aspx http://www.surgeongeneral.gov/library/bonehealth/chapter_6.html#NutritionsImpactonBon eHealthAReviewoftheEvidence Inderjeeth et al., 2010 MJA IOM & Endocrine society guidelines Kaiser Permanente, 2009 (NIH consensus conference 2000) Rianon N et al., 2011 Silverman & Christiansen, 2012, Osteop Intl Source: ASBMR using data from Looker A et al., 1998 Osteop. Intl Switzer et al.,2009 JortTrau Ward et al., 2007 Osteop Int www.nof.org/professionals/clinical-guidelines www.shef.ac.uk/FRAX 37 Rianon- HGEC-Osteoporosis, 2015 ? Questions? 38