Practical Management Of Osteoporosis CONFERENCE 2012 Education Centre, Bournemouth.19 November The following companies have given funding towards the cost of this meeting but have no input into the agenda or content. Staff from these companies will be present at the meeting and may have a stand promoting their products:
Dr Adam Wheldon Consultant Orthogeriatrician Poole Hospital
Osteoporosis Is a systemic skeletal disorder characterized by Low bone mass and deterioration of bony microarchitecture Fragile bones Increased risk of fractures, even after minimal trauma Is a chronic condition of multifactorial aetiology Clinically silent until a fracture occurs
Incidence Affects over 200 million people worldwide. Prevalence rises with age 2% women aged 50 25% women aged 80
History Age, sex, and race Family history of osteoporosis: Maternal history of fractures Early menopause & oestrogen replacement therapy Lifestyle factors associated with decreased bone density Smoking Alcohol consumption Low levels of physical activity Strenuous exercise (such as occurs in marathon runners) that results in amenorrhea Calcium and vitamin D intake
History Medications associated with bone loss Falls Risk: Poor balance Orthostatic hypotension Weakness of the lower extremity muscles, deconditioning Use of medications with sedative effects Poor vision or hearing Cognitive impairment
Examination Low body weight (BMI <19 kg/m2) Signs that might indicate a secondary cause of osteoporosis Signs that might indicate existing osteoporosis Kyphosis or dowager hump Point tenderness over a vertebrae or other suspected fracture site
Physical impact of vertebral Increased 1 yr mortality fractures Restrictive defect Age 50 Increased # risk Poor Posture Abdominal girth Back Pain Increased fall risk
Causes Primary causes: - Oestrogen deficiency - Ageing Secondary causes
Risk factors for secondary osteoporosis Endocrine: -Hyperparathyroidism, hypogonadism, hyperthyroidism, diabetes mellitus, Cushing disease, prolactinoma, acromegaly, adrenal insufficiency Gastrointestinal:-Inflammatory bowel disease, coeliac disease, malnutrition, history of gastric bypass surgery, chronic liver disease, anorexia nervosa, vitamin D or calcium deficiency Renal disease - Chronic kidney disease, idiopathic hypercalciuria Rheumatological: RA, Ank. Spond., SLE Hematologic disease -Multiple myeloma, thalassemia, leukemia, lymphoma, hemophilia, sickle cell disease, systemic mastocytosis Genetic disorders -Cystic fibrosis, osteogenesis imperfecta, homocystinuria, Ehlers-Danlos syndrome, Marfan syndrome, hemochromatosis, hypophosphatasia
Risk factors for secondary osteoporosis Other - Porphyria, sarcoid, immobilization, pregnancy/lactation, (COPD), parenteral nutrition, HIV/AIDS Medications known to cause or accelerate bone loss - Corticosteroids - Prednisolone ( 5 mg/d for 3 mo) - Anticonvulsants - Heparin (long-term) - Chemotherapeutic/transplant drugs - Hormonal/endocrine therapies (GNRH analogs) - Lithium - Aromatase inhibitors - Exemestane, anastrozole
Differential Diagnoses Hyperparathyroidism Multiple Myeloma Osteomalacia and Renal Osteodystrophy Paget Disease Other Problems to Be Considered: Metastases Leukemia Lymphoma Mastocytosis Pediatric osteogenesis imperfecta Scurvy Sickle cell anemia Homocystinuria
Investigations FBC, U/E, LFTs, Calcium, Phosphate, ALP TFT ESR Parathyroid Hormone 25-hydroxyvitamin D [25(OH)D] 24=hour urine calcium to assess for hypercalciuria Testosterone level (in males) Urinary free cortisol and tests for adrenal hypersecretion Serum and urine protein electrophoresis Antigliadin and antiendomysial antibodies for coeliac disease Bone marrow biopsy if a hematologic disorder is suspected
Investigation: Imaging Dual-energy x-ray absorptiometry (DEXA) is used to: - Establish or confirm a diagnosis of osteoporosis - To predict future fracture risk - To assess changes in bone mass over time - Is used to calculate bone mineral density (BMD) at the hip and spine. Factors that may result in a falsely high bone density determination include: - spinal fractures - Osteophytosis and - Extraspinal (eg, aortic) calcification.
DEXA:
DXA T-scores represent the number of standard deviations (SD) from the mean bone density values in healthy young adults Z-scores represent the number of SD from the normal mean value for age- and sex-matched controls. Criteria by the World Health Organization (WHO) define a normal T-score value as within 1 SD of the mean bone density value in a healthy young adult. T-score of -1 to -2.5 SD indicates osteopenia. T-score of less than -2.5 SD indicates osteoporosis. T-score of less than -2.5 SD with fragility fracture(s) indicates severe osteoporosis.
Who Needs Risk Assessment? Consider assessing Fracture risk in: All women aged >65 and men aged >75 Women between 50 65 and men 50-75 with risk factors eg frequent steroid use, high alcohol use etc People <50 if thought to be at risk Fragility Fractures
How to Risk Assess: Use FRAX (without a value for BMD) or Qfracture If fracture risk at intervention level consider DEXA Recalculate risk with FRAX Calculate the 10-year probability of a hip fracture and the 10-year probability of any major osteoporotic fracture
FRAX
Treatment Osteoporosis is typically asymptomatic until a fracture occurs Important to always Remember the risks of osteoporosis when seeing patients.
Fractured Neck of Femur 1 year mortality 20 35%
Treatment: Diet Calcium Premenopausal women and men < 50 years without risk factors for osteoporosis should receive a total of 1000 mg of calcium daily. Postmenopausal women, men > 50 years, and other persons at risk for osteoporosis should receive a total of 1200-1500 mg of calcium daily. Vitamin D Adults < 50 years should receive 400-800 IU of vitamin D 3 daily. All adults > 50 years should receive 800-1000 IU of vitamin D 3 daily.
Evidence A combination of calcium and vitamin D supplementation can reduce fracture risk A meta-analysis (n=68,517) concluded that vitamin D alone is not effective in preventing fractures, although, when administered with calcium, hip fractures and total fractures (and possibly vertebral fractures) were reduced. Ca without Vit D increased risk of MI (Bolland et al)
Treatment: Activity Weight-bearing exercise has been shown to positively affect BMD. Exercise also improves agility and balance, reducing the risk of falls. Physiotherapy can assist in developing exercise regimens and instructing patients in proper techniques.
Treatment recommendations First Line: Alendronate Second Line: Risedronate, Strontium, Raloxifene, (Ibandronate, Zolendronate) Severe Osteoporosis plus high risk for vertebral fracture: Forsteo (Teriparatide) anabolic Other: - Denosumab - Calcitonin
What are Bisphosphonates? Inhibit bone resorption Induce apoptosis of osteoclasts Prevent age related bone loss Significant reduction in vertebral fractures after 3 years in large trials
Unable to tolerate Bisphosphonate? Cannot tolerate oral bisphosphonate persistent upper gastrointestinal disturbance Have contraindications to oral bisphosphonate Acute inflammations of the gastrointestinal tract (esophagitis, gastritis, ulcerations) Certain malformations and malfunctions of the esophagus (strictures, achalasia) Inability to stand, walk, or sit for 30 minutes after oral administration Renal impairment < 35 ml/min
Other Problems! Osteonecrosis of the Jaw Dental work/poor dentition Malignancy Atypical Fracture
Suggestions of duration of bisphosphonate therapy Paucity of evidence Alendronate implicated with AF, Ca, atypical fractures but also increased life survival! Assess at 5 years with a repeat DXA if BMD stable or higher then base line have a 5 year drug holiday If BMD lower either continue or consider changing therapy
Denosumab A humanized monoclonal antibody directed against receptor activator of nuclear factor-kappa B ligand (RANKL) Denosumab decreases bone resorption by inhibiting osteoclast activity.
Denosumab Compared with placebo, denosumab decreased the risk of vertebral, nonvertebral, and hip fractures in women with osteoporosis Reduction in fracture rate 68% vertebra 40% hip 20 nonvertebral
Hormone replacement therapy (HRT) Was once considered a first-line therapy for the prevention and treatment of osteoporosis in women. HRT can reduce fractures. However, HRT was associated with an increased risk of breast cancer, myocardial infarction, stroke, and venous thromboembolic events HRT is approved for management of menopausal symptoms and prevention of osteoporosis. It is no longer recommended as a treatment of osteoporosis in postmenopausal women.
Summary: Osteoporosis is common It increases morbidity and mortality There are effective treatments available Prevention is key!
Thank you