Kristen M. Nebel, DO PENN/ LGHP Geriatrics 10/3/17 Temple Family Medicine Review
OBJECTIVES Define Revised 2017 American College of Physician Recommendations Screening, Prevention and Treatment Application in Special Circumstances/ considerations
IMPACT 54 million in US; 200 million worldwide 50% of Americans over 50 at risk for osteoporotic fracture Increased morbidity/ mortality with hip fx Risk of 2 nd vertebral fracture within one year is 20% Injuries from falls make up 40% of ECF admissions Guidelines Annals.org 2017 ACP Clinical
BONE PATHOPHYSIOLOGY Normal: Osteoclasts: dissolve protein matrix and collagen. Resorption markers: N-telopeptide and C-telopeptide. Serum and Urine NTX Osteoblasts: synthesize new bone. Formation markers: bone-specific alkaline phosphatase and osteocalcin
OSTEOPOROSIS: CONSEQUENCES Reduced QOL Increased mortality Only 40% return to prior level of function Depression Multiple thoracic fractures restrictive lung disease L b f t ti ti bd i l i di t ti d d tit d l Lumbar fractures constipation, abdominal pain, distention, reduced appetite, and early satiety
RISK FACTORS FOR OSTEOPOROTIC FRACTURE BMI<21 Medications Personal history of fractures as adult First-degree relative with fragility fracture 50% greater if 1 st degree relative had + fx 127% greater if parent had hip fx Current smoking Age Menopause, Hypogonadism Ethnicity Nutrition Decreased activity ETOH Dementia Poor health Recent falls
MALE OSTEOPOROSIS Morbidity and mortality much higher in men than women with osteoporotic fracture Secondary causes more common accounting for 50% ETOH (15-20%), glucocorticoid (20%), and hypogonadism (15-20%)
SCREENING Annual height measurement : loss of 2 cm or more Dual-energy x-ray absorptiometry Women age 65 and older and men age 70 and older Postmenopausal women and men above age 50 69 with risk factors Postmenopausal women and men age 50+ with h/o adult age fracture Medicare coverage for: women 65+ q 2 yr Bony abnormalities; glucocorticoid medication; HPTH; abnormal x-ray; estrogen deficiency, vertebral fracture ICD-10 code : M85.88 Other specified disorders of bone density and structure, other site
DIAGNOSIS CRITERIA Definition: A disease characterized by low bone mass and microarchitechtural deterioration of bone tissue leading to enhanced bone fragility and a consequent increase in fracture incidence. Dexa WHO: BMD T-score of -2.5 or less Any vertebral fracture = Osteoporosis
OSTEOPOROSIS EVALUATION Labs CMP, phosphate, CBC, ESR, TSH/FT4 Testosterone/ Estrogen SPEP/UPEP 24 hour urine for calcium and creatinine 25-OH Vit. D Intact PTH Biochemical i markers of bone turnover Imaging X-rays not a primary work-up
INITIATING THERAPY- OSTEOPOROSIS ACP Recommendation #1: Offer treatment of Alendronate, Risedronate, Zoledronic acid, or Denosumab to women with known osteoporosis to reduce risk of hip and vertebral fractures (strong; high-quality) ACP Recommendation #2: Treat with medication for duration of 5 years (weak; low quality) ACP Recommendation #3: Offer bisphosphonates to men with osteoporosis to reduce risk of vertebral fracture (weak; low quality) ACP Recommendation #5: Against use of menopausal estrogen or estrogen-progesterone or raloxifene in women (strong; moderate quality) Annals.org 2017 ACP Clinical Guidelines
INITIATING THERAPY- OSTEOPENIA ACP Recommendation #6: Clinicians should make decision to treat osteopenic women 65+ yo at high risk for fracture based on shared decision-making [discussion of FRAX patient preferences, fracture risk profile, and benefits/ harm/ cost of treatment] ](weak; low quality) WHO s 10-yr risk assessment of osteoporotic fracture using 9 clinical risk factors +/- hip BMD Therapy indicated if 10-yr. risk of hip fracture >/= 3% or other major fracture risk >/= 20% (Tosteson et al. Osteop. Int. 2007) FRAX calculator Free mobile APP: Dr. FRAX
NON-PHARMACOLOGIC TREATMENT Calcium : 1,200 mg/ day via diet and supplement Milk (8 oz) or Yogurt (6 oz) = 300 mg; incidental 250 mg/ day in typical diet Vitamin D: 800-1,000 IU/ day; replete if < 30. Augments activity of bisphosphonates Muscle- strengthening and weight-bearing exercises Tai Chi Home safety assessment Wean off psychotropic medications Stop tobacco and alcohol
PHARMACOLOGIC OPTIONS Antiresorptives Estrogens/HRT-- NO Selective-estrogen receptor modulators (SERMS)-- NO Calcitonin NOT a first line Bisphosphonates YES Zoledronic Acid --YES Anabolic PTH Severe, refractory only Antibodies Desonumab YES Do NOT combine medications
BISPHOSPHONATES First-line for most NNT Vertebral fracture; hip fracture; cost/ year Alendronate 15; 91 ; $100/ year Risendronate 20; 91 ; $1,330/ year Ibandronate 21; no reduction Avoid if: Unable to follow dosing and administration instructions Hypocalcemic CrCl < 30 ml/min Safe to hold short-term
BISPHOSPHONATE SIDE EFFECTS Gastric irritation and ulcers ONJ, A fib, Atypical fractures (to follow) Infusions:1 1 st infusion = acute phase reactants (arthralgia, HA, myalgia, fever)- may pretreat with Tylenol GI upset Risk of side effects tapers with subsequent dosing
OSTEONECROSIS OF THE JAW American College of Rheumatology position paper Case review: 60% following oral surgery or dental extraction. 94% of the cases occurred with IV bisphosphonates (Pamidronate or Zoledronic acid) 85% had MM or metastatic breast CA to bone. Non-cancer patients and oral meds not considered d risk factors 0.04% incidence with oral bisphosphonates 93. J Maxillofac Oral Surg 2014;13:386- To avoid ONJ: treat infections and obtain routine dental care prior to therapy Appearance of intraoral lesion with exposed bone +/- painful ulcers, ragged
ATRIAL FIBRILLATION Conflicting reports from population-based case controlled studies Reanalysis of several trials did not show increased risk of atrial fibrillation. Current recommendations are not to withdraw therapy
ATYPICAL HIP FRACTURE If radiographic changes noted: STOP bisphosphonate Swedish population-based observational study of subtrochanteric (shaft) fractures Concluded the absolute risk of atypical fracture was small compared to benefits of drug in those at high risk for OP fracture ( Schilcher et al NEJM 2011)
ZOLEDRONIC ACID IV medication for those unable to take oral bisphosphonate NNT vertebral fracture 14 ; hip fracture 91; cost $300 Duration: 3-5 years (Level C; expert opinion) or 6 year in high-risk patient Rheum Int 2010; 30:863-9. Avoid in: Hypocalemia CrCl < 30 ml/min Side effects: Flu-like reaction Osteonecrosis in up to 12% Musculoskeletal pain ARF N Eng J Med 2012;366:2051-3.
DENOSUMAB (PROLIA) RANKL Inhibitor: inhibits osteoclasts NNT vertebral fracture 21; hip fracture 200; cost $2,100/ year Duration: 5 years (Level C; expert opinion) Fracture risk maintained up to 2 years after therapy, but BMD rapidly declines after completion Safe in CKD I-IV Avoid in Hemodialysis, hypocalcemia Side effects: May inhibit fracture healing increase in infections Jaw osteonecrosis in up to 1.7%
PTH (1-34): TERIPARATIDE (FORTEO)&ABALOPARATIDE (TYMLOS) Anabolic: Stimulates osteoblast activity-> increased trabecular bone density Treatment of high risk postmenopausal and male OP T-score of -3.5, fractures + T-score -2.5, and those who fail 2 yrs of bisphosphonate therapy Fracture on bisphosphonate Duration: 2 years due to concern for osteosarcoma in non-human trial. Follow with Bisphosphonate
PTH (1-34): TERIPARATIDE (FORTEO)&ABALOPARATIDE (TYMLOS) NNT Vertebral fracture; nonvertebral fracture; hip; cost/ year Abaloparatide 28; 50; no reduction; $19,500 Teraparatide 11; 33; no reduction; $36,000 Fracture Prevention Trial : 20mcg/d reduced vertebral and non-vertebral fractures by 65% and 53%, respectively after 18 months Review of FPT to assess safety and efficacy in women 75+ compared with younger women found that lumbar and femoral neck BMD both increased significantly and new vertebral fractures risk NNT =11 (Boonen et al. JAGS 2006)
PTH (1-34): TERIPARATIDE (FORTEO)&ABALOPARATIDE (TYMLOS) Side effects: dizziness, leg cramps, increase in severity of patient-reported back pain, (osteosarcoma seen in rat trials) Avoid in: Paget s disease of bone, prior radiation therapy of the skeleton, bone metastases, t hypercalcemia, or a h/o skeletal malignancy CKD: Teriparatide- use with caution in moderate impairment Abaloparatide- no dose adjustment needed in study n=31 Product Info Tymlos. Radius Health Inc. April 2017
MONITORING AND FOLLOW-UP Women can have reduced fracture rates from anti-resorptive therapy even without increased BMD. No recommendations for BMD in men on treatment. 2017;166:818-39 Annals Int Med 2 year Dexa not indicated after normal screening Dexa or during treatment Only 10% of women had progression to osteoporosis in 15 years A BMD in untreated patients has limited value in predicting fracture when Dexa done within 4 years 2013) (JAMA Sept
MONITORING AND FOLLOW-UP ACP Recommendation #4: Against Dexa during 5-year pharmacologic treatment period for osteoporotic women (weak; low quality) At 5 years: can STOP bisphosphonate treatment if no fracture and stable Dexa Continue after 5 years if patient remains high risk for fractures
MONITORING AND FOLLOW-UP A fracture on bisphosphonate = failed treatment STOP med Evaluate for secondary cause Change to Forteo, Tymlos, or Prolia based on independent factors Secondary workup: Medications Renal insufficiency secondary HPTH Cushing s Hyperthyroid Multiple myeloma Osteomalacia Paget s Dz GI malabsorption / celiac Mets to bone
CONTINUE TREATMENT OR NOT? Tools to help If starting Bisphosphonate consider baseline serum NTx Follow yearly NTx: If NTx < 40 nmol BCE/mmol Cr= effective treatment If at end of treatment: stop therapy and continue Calcium, Vitamin D, and exercise If NTx > 40 + high risk factors consider continuance/ restart of anti-resorptive or change to Prolia Vertebral x-ray New fracture indicates need to restart or change treatment Dexa monitoring can be q 2-4 years after treatment completion or initiation of chronic high risk med.
RESTART BISPHOSPHONATE? Consider if: Worsening Dexa after any treatment ends New risk factor develops
TREATMENT CONSIDERATIONS IN CKD Bisphosphonates not approved for use with GFR < 35. Post-hoc analyses show off-label use may be safe and effective for Risedronate, Alendronate, and Raloxifene in GFR 15-30 for limited time of 3 years. IN HD patients: 50% of dose for short duration. Calcitonin is safe Desonumab safe with GFR 15 + for at least 3 years Teriparatide is safe for GFR 30+ unless presence of hyperpth or hypercalcemia Tymlos may be safe < GFR 30, but further data needed
THE END QUESTIONS AT NEXT PANEL