Osteoporosis in primary care WAPA 2013 Ina Oppliger, M.D. Tacoma Rheumatology
The bottom line 1. Osteoporosis is a problem we can and should do something about 2. Bone density testing should be done on all women over 65 and anyone who has a low impact fracture 3. Prevention involves both improving bone density and reducing falls 4. Drug therapy should be targeted to those at high risk of fracture within 5 years.
The problem Lifetime risk (women) any fracture- 50% hip fracture- 15% US cost 17-20 billion/year (CHF:8 billion) What happens if you have a hip fracture after age 50? 24% die within 1 year of fracture 40% move from independence to LTC
Preventing fractures 1. Improve bone density and structure -minimize drugs that reduce bone density -weight bearing exercise - vitamin D and calcium supplementation - drug therapy for those at highest risk 2. Reduce Falls
Bone Density and structure as a risk factor for hip fractures
Who to Screen for low bone density? by Dual energy X-ray absorptiometry (DEXA) Population Screening recommendation Women aged > 65 DEXA Recommended for all Women aged 60 64 Men and Women aged <59 Consider DEXA if patient weighs 60 kg (<132 lb) or at high risk of osteoporosis secondary to certain medical conditions or drugs DEXA not recommended unless patient at high risk of osteoporosis secondary to certain medical conditions or drugs). Men and women of any age with low impact fracture In appropriate clinical circumstances, osteoporosis may be assumed, but if unclear, DEXA recommended.
High Risk Conditions for low bone density Anorexia nervosa Cushing s syndrome Cystic fibrosis Diabetes, type 1 Gaucher s Hemochromatosis Chronic liver disease Chronic renal insuff. Hyperparathyroidism Hyperthyroidism Hypogonadism Hypophosphatasia Marfan s Malabsorption myeloma Osteogenesis imperfecta Inflammatory arthritis Rickets Spinal cord injury Systemic mastocytosis Drugs Anticonvulsants Steroids Heparin High dose thyroid Gonadal hormone inhibitors
Keep it simple Just do the DEXA! Low hanging fruit Age 65 or more History of previous low impact fracture Chronic steroid use >5mg for >3 months
Interpreting DEXA results T-score: compares your bone density to a healthy young person (~30 year old) of same gender and race. Z- score compares your bone density to a person your own age FRAX score: uses the bone density at the femoral neck and other risk factors to estimate your risk of fracture over the next 10 years
Bone density report for a 65 year old woman Femoral neck: T score -1.5, Z score 0.1 Lumbar spine: T score -1.8, Z score 0.3 Interpretation: Osteopenia, increased risk of fracture
Interpreting DEXA results: Check the images, don t trust the lumbar spine Report: L1-4: normal bone density
Interpreting the DEXA: Heed the Z score
Dexa Interpretation Pearls 1. Spines are suspect: Bone spurs (and compression fractures) make the spine look good! Ignore the spine in elderly patients. 2. Check the neck: the femoral neck T score is one of the key sites to evaluate osteoporosis 3. Heed the Z: A low Z score suggests something more than just aging is affecting the bone. Do some lab work if Z score <-2.0
BONE DENSITY AND FRACTURE RISK are not the same thing!
Risk factors for hip fracture (Cummings, et al) Osteoporosis (Low BMD) Age >79 Any Fx after age 50 Weight<132 lb Maternal Hip Fx Medications that lower bone density On feet<4 hours/day No walking for exercise Low calcium intake Fall risk Inability to rise from chair without use of arms Poor vision Heart rate>80 Seizure disorder >2 cups caffeine/day Benzodiazepine Rx Fair/poor health History of falls
Google frax calculator FRAX calculation combines bone density with other risk factors to provide an estimate of fracture risk National Osteoporosis Foundation guidelines: treatment advised if 10 year risk >20% for any fracture or >3% for hip fracture
Treatment of osteoporosis (low bone density or previous low impact fracture) Minimize medications that lower bone density Calcium and Vit D supplementation Weightbearing exercise Medications Bisphosphonates (alendronate, risedronate, ibandronate, pamidronate, zoledronic, etidronate) HRT or SERMS Calcitonin Denosumab Teriparatide
Drugs that lower bone density Alcohol Tobacco Corticosteroids Excessive thyroxine Depo- Provera Gonadal hormone antagonists PPI Anticonvulsants Heparin SSRI? Drugs that increase falls Alcohol Sedatives Antidepressants Hypotensive agents
November 2010 consensus report How much calcium and D per day?
Calcium Supplementation RDA=800-1,300 mg/day. Average dietary intake~600mg/day Whole Milk (1 cup) 300mg Skim milk (1 cup) 300mg Cheddar Cheese (1.5 oz) 300mg Yogurt (8 oz) 300 mg Firm tofu (1/2 c) 300mg Frozen yogurt (1/2c 60mg Ice cream (1/2c) 80mg Cottage cheese (1/2 c) 60mg White bread, 1 slice 70mg
Prescribing Calcium Supplements Calcium citrate is more expensive, but generally better tolerated and is better absorbed in the absence of stomach acid
Calcium supplements Calcium carbonate better absorbed with food Dissolution of calcium tabs varies Calcium citrate better absorbed in achlorhidria Calcium inhibits absorption of iron and thyroid supplements Calcium should be taken in divided doses, but if take just once, maybe more effective at bedtime Kidney Stones: decreasing salt and protein intake reduces calcium oxalate stones. Measure urine calcium. If hypercalciuric, consider low dose thiazide.
What about Vitamin D? All who drink this remedy are cured, except those who die. Thus, it is effective for all but the incurable. - Galen, ca 150 A.D.
What s the right level of vit d? NHANES 13,331 adults 8.7 years follow up 26% increase in all cause mortality if<18 Melamed et al 2008
UVB290-315nm cholecalciferol UVR yeast
Little production above the 37 th parallel (UVB 290-315)
Vitamin D: bottom line(for now) adults in the pacific northwest could take 600-1000 units of Vit D3/day. It might be good for them. Nobody is sure what the right blood level of Vit D is, but <20 ng/ml of 25 (OH) Vit D is probably too low. Start a supplement for a few months before checking a level (60-120 days), unless you are starting a bisphosphonate.
MEDICATIONS FOR OSTEOPOROSIS Fracture reduction Bisphosphonates: 36-70% decrease in fracture risk Denosumab(Prolia):19-68% decrease in fracture risk Teriparatide (Forteo): 53-65% decrease in fracture risk HRT/SERMS (23-55%?) Calcitonin (33%?))
Bisphosphonates Alendronate (Fosamax): 70 mg p.o. every week Risedronate (Actonel): 35 mg p.o. weekly Zolendronic acid (Reclast): 5mg IV once a year Ibandronate (Boniva) 3mg IV every 3 months Or 150mg p.o. monthly Plan to treat for 5 years, then reassess
Bisphosphonates Cochrane review: analysis of studies of alendronate therapy in women>age 62 Secondary prevention: Alendronate given to women over age 62 with T<-2.0 or prior low impact fracture resulted in: - 45% fracture reduction over 3 years -NNT to prevent a vertebral fx: 16 -NNT to prevent a hip fracture: 100 NNT falls as risk of fracture rises ( NNT at age 80= 21 for hip fx, 12 for vertebral fx) Benefit appears in first year of therapy
Bisphosphonates -good news: overall mortality. NEJM 2007
Bisphosphonates: the bad news 1. Gastrointestinal adverse effects 2. Hypocalcemia 3. Osteonecrosis of the jaw As of 2007, 67 cases reported with oral bisphosphonates Incidence less than 1 IN 10,000 4. Atrial fibrillation (?) 5. Musculoskeletal pain 6. Iritis 7. IV forms: acute renal failure, hypersensitivity reactions Problems in younger patients Contraindicated in pregnancy! Stays in skeleton for decades- unknown risks Inhibits remodeling May reduce response to bone formation stimulating drugs
How long to treat with a bisphosphonate? Atypical fx of femur If you treat beyond 5 years: - Some continued increase in bone density years 6-10 - Some additional decrease in vertebral fractures - No additional decrease in hip fractures - Increasing risk (though still small) of atypical femur fx If you stop at 5 years, benefit in regard to reduction in hip fx is maintained over the next 5 years
Bisphosphonates briefly Prevent resorption/remodeling of bone Remains in bone for many years, may recycle in circulation Reduces fracture risk by 40-50% (USPSTF) First, check: calcium, creatinine, Vit D Always accompany with calcium and vit D supplementation Contraindicated in renal insufficiency (CC<35) Re-evaluate at 5years
SERMs Raloxifene, Tamoxifen Raloxifene 60 mg/d Less effective than bisphosphonates, No reduction in hip fractures Decreased breast Ca risk, no increase in uterine Ca, Ineffective in premenopausal women Thrombotic risk similar to HRT Hot flashes in 15-25%,muscle cramps, edema
Calcitonin nasal spray 200U-one spray daily few side effects minimal effect on bone density, no reduction in hip fractures may provide analgesic effect in acute compression fractures Metanalysis of 4 trials showed compared with placebo, calcitonin decreased pain by the end of week 1 mean of -3.4 points on 10-pt scale Osteoporos Int. 2012; 23(1):17
Denosumab: Monoclonal antibody against RANKL Dosage: 60mg SQ every 6 months Advantages: useful in renal insufficiency, bisphosphonate failure Adverse effects: hypocalcemia, cellulitis, eczema, arthralgias Denosumab vs placebo:effect on fracture rate cummings et al NEJM 2009
Teriparatide Recombinant 1-34 PTH-FDA approved 12/02 20mcg subq daily, limit treatment to 2 years Anabolic: vertebral BMD increases of 8.6% over 2 years, femoral neck increased by 3.6%, vertebral fracture reduction >50% in 21 months Osteosarcoma in 50% of rats- high dose Adverse effects: Hypercalcemia, increased uric acid, hypotension Cost: $12,000/year. Effect short lived: Must follow with an antiresorptive drug
Lab testing
Laboratory evaluation for osteoporosis Creat Calcium 25 OH Vit D PTH, intact TSH if on treatment Testosterone (males) CBC SPEP/UPEP LFTs Phosphate Alkaline phosphatase 24 hr. urine Calcium N telopeptide LOW Z score : more investigation
Who to treat for osteoporosis? Treatment algorithm
Treatment for dummies Age>65 and T score <-2.5 History of low impact fracture and T score<-2.5 bisphosphonate best choice if over age 65
A humble proposal: Osteoporosis patients over age 65 1. Start Calcium (500 BID) and Vit D (1000U) 2. Send lab for Calcium, Creat, 25(OH) Vit D TSH if on T4, testosterone if male 3. If calcium and creat are normal and the patient can swallow easily and sit upright for 1 hour, then start alendronate 70mg once a week. 4. Discuss fall prevention, including exercise, grab bars, eye exams 5. If Vit D is less than 20: give 50,000 U Vit D 2 weekly for 8 weeks or 2,000 U Vit D3/day, recheck in 3 months 6. Schedule a followup to check on compliance
Fall prevention Environment: Lights, Rails, Rugs, Pets, Stairs, Bathtubs Assists: Walker, Cane, Glasses, shoes Meds: sedatives, antidepressants, orthostatic hypotension, ETOH Hip Pads: 1-800-930-9255 safehip $89.00 per pair (sewn in)
Exercise 30 minutes a day Weight bearing Dance, Tai-Chi, Walking Getting up to the bathroom reduces rapid loss associated with bed rest.
Special Cases Osteoporosis in men: 20% of hip fractures occur in men. Start screening at age 70(?)Use female reference for T score or 3 if male reference group.. Longterm steroids: Rapid bone loss (lose 8% of trabecular bone at 20 weeks of 7.5mg/day) Increase in vertebral fractures even before measurable bone loss occurs. Consider empiric bisphosphonate therapy for age >65.
The bottom line, again Osteoporosis is a problem We can and should do something about it Measure bone density in women over 65 and anyone with a low impact fracture Reduce fracture risk by improving bone density and by preventing falls Drug therapy should be targeted to those at high risk of fracture in the next 5 years
Tough case? Call your friendly rheumatologist or endocrinologist