Presentation on theme: "Richard S. Pope MPAS, PA-C DFAAPA Arthritis Center of CT Waterbury, CT Danbury Orthopedics Danbury, CT OSTEOPOROSIS CASE STUDIES Where to use what FDA."— Presentation transcript:
Richard S. Pope MPAS, PA-C DFAAPA Arthritis Center of CT Waterbury, CT Danbury Orthopedics Danbury, CT OSTEOPOROSIS CASE STUDIES Where to use what FDA approved Medicine and When.
Faculty Disclosures Amgen- Advisory committee denosumab URL Pharma-Advisory committee and speaker’s bureau colchicine UCB Pharma-Speaker’s Bureau certolizumab Takeda-Speaker’s bureau febuxostat
By using case studies at the end of this session the participant will be able to choose treatment or not based on the scenarios listed below: 1.Perimenopausal osteopenia with a family history of osteoporosis (To treat or not to treat?) 2.Osteoporosis by BMD without fracture in a sixty five year old female 3.Recent wrist fracture in a 65 year old with low bone density (Treating based on fracture and not BMD) 4.Severe osteoporosis with a T-score of <-3.0 with fractures (Case for anabolic treatment) 5.Osteoporosis in a PMP female with CKD stage 4 (15-29 ml/min/1.73²)
Case 1 Perimenopausal osteopenia with a family history of osteoporosis (To treat or not to treat?) 56 year old W/F routine GYN appt. and follow up of stage II b breast CA. Rxed with surgery Xs 2 for lumpectomy at age 44 Six weeks of localized radiation to right breast Chemotherapy 6 rounds of epirubicin, cytoxan and 5FU, adjuvant therapy of aromatase inhibition Xs 2 yrs. Tamoxifen for first three years. No menses after chemotherapy age 44 BMD T-score of -2.1 in femoral neck No fractures as an adult. Mother treated for OP at age 88 GM fractured hip
Case 1 Perimenopausal osteopenia with a family history of osteoporosis (To treat or not to treat?) Secondary work up for OP included: – CBC, comp. chem profile, 24 hr. urine ca+, celiac panel, Vit. D 25 OH D level, protein electrophoresis Results – + for Vit. D of 13ng/ml – 5’ 5’’ 147 lbs. FRAX?
Secondary osteoporosis FRAX calculator Enter yes if the patient has a disorder strongly associated with osteoporosis. These include type I (insulin dependent) diabetes, osteogenesis imperfecta in adults, untreated long-standing hyperthyroidism, hypogonadism or premature menopause (<45 years), chronic malnutrition, or malabsorption and chronic liver disease
Case 1 Perimenopausal osteopenia with a family history of osteoporosis (To treat or not to treat?) How would you manage this patient? 1.Because of her + family history and low Vit D level would go ahead and treat with FDA approved meds. 2.Replete patient with high doses of Vit D 3.Recommend weight bearing exercises, Ca+ 1200mg/day and vitamin D 800 IU/day 4.Re-check the Vit D level in three months after replacement.
Case 2 Osteoporosis by BMD without fracture in a sixty five year old female 65 year old comes for routine physical and you note that she has not had a prior BMD DXA PMHx: GERD, Barrett’s esophagus Hypertension OP risk factores: no hx of fx as an adult No parental history of hip fracture but mother had multiple compression fractures and associated height loss She smokes about 15 cigarettes/day and unable to give up the habit Drinks 2+ glasses of wine daily
Case 2 Osteoporosis by BMD without fracture in a sixty five year old female MEDs: -losartan 50mg -esomeprazole 40mg Barrett’s esophagus -Ibuprofen 400 prn HA and joint pain -MVI (200iu Vit D2 ergocalciferol) -Calcium carbonate 1,000mg -Vit D3(cholecalciferol 1,000 IU daily)
Case 2 Osteoporosis by BMD without fracture in a sixty five year old female Lab work up shows Vit D 21ng/ml otherwise negative BMD T-score in the lumbar spine is -2.5 To treat or not to treat? 1.Pt is at risk for esophageal side effects 2 nd to GERD 2.Barrett’s esophagus As a result would avoid oral bisphosphonates
Case 2 Osteoporosis by BMD without fracture in a sixty five year old female Management options Pt preference (discuss pros and cons) Raloxifene STAR trial, RUTH trial IV bisphosphonates: -zoledronic acid (data in spine/hip/non-vertebral) -ibandronate(data for spine not hip)
CASE 3 Recent wrist fracture in a 65 year old with low bone density (Treating based on fracture and not BMD) Sally, age 65, has been concerned over her bone health as a result of fracturing her wrist last month. She is referred to you as her PCP for evaluation by her orthopedist. She twisted her foot and fell on an outstretched hand and sustained a Colles fracture. History: 1.No parental history of fracture 2.She did smoke but has not since she was 45 3.She drinks 1-2 glasses of wine every night. Denies alcohol abuse 4.She gets plenty of sunlight and was just in FL with her 3 grown daughters. 5.Other than her wrist fracture no other fractures as an adult.
CASE 3 Recent wrist fracture in a 65 year old with low bone density (Treating based on fracture and not BMD) PE: height 5’6” stadiometer 1.5 inch loss Weight 176 lbs Very mild kyphosis Gait and stability tests good. Gets up without arm rests
Case 3 What would you do next to work up this patient? CHOOSE AS MANY AS ARE CORRECT 1.BMD 2.Chemistry profile, CBC, Vit D 25 level etc. 3.Dorsal spine x-ray 4.Use FRAX™ Calculator
CASE 3 Recent wrist fracture in a 65 year old with low bone density (Treating based on fracture and not BMD) DXA BMD femoral neck T-score -2.2 Laboratory work-up Vit D 28ng/ml 24 hour urine calcium <200mg/dcl (nml) iPTH and ionized Calcium (wnl) Celiac panel negative SPEP normal D-spine x-ray negative for morphometric fracture
Case 4 Severe osteoporosis with a T-score of <-3.0 with fractures (Case for anabolic treatment) 79 year old male Asymptomatic compression Fxs T-10 and L-4 Parkinson’s Disease Recent wrist fracture T-Scores: – Spine -3.0 T score at L-S 2-4 – Hip -2.8 Severe osteoporosis (osteoporotic fx and BMD -2.5 or worse)
Case 4 Severe osteoporosis with a T-score of <-3.0 with fractures (Case for anabolic treatment) Treatment considerations 12 fold increased risk for subsequent vertebral fxs. Is at extremely high risk for falls 2° Parkinson’s Needs fall protection, home inspection for loose rugs and well lit bathrooms especially at night. Needs aggressive therapy for severe osteoporosis.
Increased spinal BMD 9% 96% of women showed an increase in BMD Increased femoral neck BMD 3% Reduced new/worsening back pain Reduced fracture-associated height loss Reduced risk of new vertebral fractures by 65% Reduced risk of moderate and severe vertebral fractures by 90% Reduced risk of non-vertebral fragility fractures by 53% Studies are too small to evaluate effect on hip fracture Teriparatide rhPTH [1-34] 20 mcg SQ qD Neer et al. N Engl J Med 2001; 344:1434-41
Case 5 Osteoporosis in a patient CKD stage 4 86 year old female s/p CVA uses cane and has a dense left hemiparesis Her BMD show a -3.1 BMD in her left hip She has a history of borderline renal function and has an eGFR of 33ml/min. She is hypertensive, diabetic and on lisinopril, insulin glargine, pravastatin, baby ASA and coumadin.
Case 5 Osteoporosis in a patient with renal disease Labs: Vit D 36ng/ml iPTH and ionized Ca+ wnl 24 hour urine Calcium wnl SPEP and Celiac panel are normal Cockcroft-Gault method GFR 33mls/minute Bisphosphonates are renally cleared and are contraindicated below 35ml/minute GFR www.mdcalc.com/creatinine-clearance-cockcroft-gault-equation
Case 5 Osteoporosis in a patient with renal disease Treatment Recommendations Denosumab—is not renally excreted and therefore no dosage adjustments are required for patients with chronic kidney disease. (creatinine clearance <30 mL/min). Patients in this population are more likely to have hypocalcemia and this is a contraindication to its use. Screening labs should be performed for ca+ level. Phosphorus and mg+ and repeat calcium in renal pts is recommended ten days after dosing. If serum calcium is low calcium levels should be corrected. If pt does not have renal disease serum ca+ not required. Denosumab for osteoporosis uptodate version 19.2 Accessed 7-11-2011
RANKL Antibody/RANKL: Activation Of Osteoclasts Activated osteoclast CFU-M Pre-fusion osteoclast Multinucleated osteoclast Bone OB Growth factors Hormones Cytokines RANKOPGRANKL RANK = Receptor Activator of Nuclear factor Kappa B RANKL = RANK Ligand CFU-M = Colony-Forming-Unit Macrophage OPG = Osteoprotegerin Adapted from Boyle, et al. Nature 2003;423:337 OPG Denosumab Y Y Y Y Y Y Y Slide courtesy of Steve Harris MD
Safe and effective therapies are available Antiresorptive agents Prevent bone loss and preserve architecture Improve quality of bone Reduce the risk of vertebral fractures (all agents) Alendronate, risedronate and zoledronic acid proven to reduce the risk of nonvertebral and hip fractures Anabolic agent: rhPTH [1-34] (teriparatide) Increases bone density and size Improves quality of bone Reduces the risk of vertebral and nonvertebral fractures; no hip fracture data RankL inhibitors (denosumab) Inhibits function and survival of osteoclasts via RankL inhibition Prevents bone loss by decreasing bone turnover Reduces risk of vertebral, non-vertebral and hip fractures Indicated for treatment of PMP only (July 2011) Patient factors determine the most appropriate drug to use Treatment: Summary
1 AWP (Average Wholesale Price) varies by region and distributor * Medi-Span Drug Data. Price Rx® Prescription drug database (Accessed 30 October 2009) Red Book: Pharmacy’s Fundamental Reference. Thomson Medical Economics: Montvale, NJ. 2007. Drugs to Treat Osteoporosis Cost per Effect on Fracture Risk Agent year 1 Vertebral Nonvert Hip Raloxifene $976* -- -- Calcitonin $1,517* -- -- Brand alendronate $1,103 Generic alendronate$108 Risedronate $1,110 Ibandronate (oral) $1,024 -- -- Ibandronate (IV) $1,938 Zoledronic acid $1,249 Teriparatide $9,786 -- : antifracture efficacy proven in clinical trial --: antifracture efficacy not proven in clinical trial
Case Summaries 1. Perimenopausal female with a low bone density. FRAX calculator and treat with life style and Vit D and Ca+. 2. OP by lumbar T-score and no fx–history of Barrett’s, GERD. Avoid oral bisphosphonates, consider IV bisphosphonates or raloxifene. 3. Wrist fracture in a sixty five year old. Fracture trumps the DXA. FDA approved meds.
Case Summaries Continued 4. Severe OP multiple compression fxs, T-score -3.0. Case for anabolic agent. 5. OP in a CKD stage 4- RankL inhibition in renal pts where bisphosphonates are contraindicated