Current Trend in Osteoporosis Management for Elderly in HK- Medical Perspective Dr Dicky T.K. Choy Physician Jockey Club Centre for Osteoporosis Care and Control, CUHK Osteoporosis Global public health problem It is an intermediate outcome for fractures and is a risk factor for fracture just as HT is for stroke ** The majority of fractures, however, occur in patients with low bone mass rather than osteoporosis 1 2 Old Definition of Osteoporosis A systemic skeletal disease characterized by low bone mass and micro-architectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. Current Definition of Osteoporosis Osteoporosis is defined as a skeletal disorder characterized by compromised bone strength predisposing a person to an increased risk of fracture. Bone strength primarily reflects the integration of bone density and bone quality. Normal bone Osteoporosis Conference Report from the Consensus Development Conference: NIH Consensus Development Panel on Osteoporosis JAMA 285:785-95; 2001 Am J Med 94: 646-650, 1993 3 4
A diagram of a cutting cone with osteoclasts resorbing bone followed by osteoblasts depositing new osteoid, which subsequently becomes calcified Pathophysiology 5 6 Bone remodeling Vertebral Fracture Bone loss occurs when this balance is altered, resulting in greater bone removal than replacement This imbalance occurs with menopause and advancing age. Hip Fracture Colles Fracture 7
Epidemiology All Hip Spine forearm Women 40% 18% 16% 16% Men 13% 6% 5% 3% 9 (Melton, 1992) 10 Asia 54% Hip fracture for men and women in 2050 Men (1.8 million) Others 8% Latin America 6% Middle East 8% Europe 11% North America 13% Asia 51% Others 6% Latin America 12% Women (4.5 million) Middle East 6% North America 12% Europe 12% 11 Adjusted Rates (100,000) Age-adjusted incidence rates in women 600 500 400 300 200 100 0 535 459 442 269 US (White) Hong Kong Singapore Thailand 218 Malaysia 12
Adjusted Rates (100,000) Age-adjusted incidence rates in men 200 150 100 50 187 180 164 114 0 US (White) Hong Kong Singapore Thailand 88 Malaysia 13 Age specific incidence rates for hip, vertebral, and distal forearm fractures in men and women Men Women Incidence/100,000 person-yr 4000 3000 2000 1000 0 Hip Hip Vertebral Vertebral Colles Colles 35-39 85 85 Age group, yr 14 Incidence of hip fracture in Hong Kong women 2500 2000 1995 Incidence of hip fracture in Hong Kong men 1200 1985 1995 Per 100,000 1500 1000 500 1985 1966 Per 100,000 800 400 1966 0 50-59 60-69 70-79 80+ Age 15 0 50-59 60-69 70-79 80+ Age 16
Direct cost for osteoporotic fractures Mortality and morbidity due to hip fracture is high USA Hong Kong (hip fracture) Women 11.1 billion 2.9 billion Men 2.7 billion 1.1 billion 10-20% excess mortality within 1 year Up to 25% remain in long term nursing home care Only 40% fully regain their pre fracture level of independence 17 18 Mortality and morbidity due to vertebral fracture is also high Significant complications including back pain, height loss and kyphosis Limited activity including bending and reaching May result in restrictive lung disease if multiple thoracic fractures Lumbar fracture may alter abdominal anatomy Approach to the Diagnosis and Management 19 20
Comprehensive approach Detailed history (clinical risk factors assessment including fall risk assessment ) Bone mineral density (BMD) assessment Establish fracture risk using WHO 10-year estimated fracture probability Risk factors included in the WHO 10- year Fracture Risk Assessment Model Age Gender Personal history of fracture Parental history of hip fracture Low body mass index (BMI) Use of oral glucocorticoid Secondary osteoporosis (e.g RA ) Current smoking Alcohol intake 3 or more drinks/day Femoral neck BMD 21 22 Risk Factors for Falls 1. Environmental 2. Medical 3. Neuromuscular 4. Fear of falling Environmental Low level lighting Obstacles in the walking path Lack of assist devices in bathrooms Slippery outdoor conditions 23 24
Medical Neuromuscular Age Arrthymias Poor vision Urgent urinary incontinence Previous fall Orthostatic hypotension Medications ( narcotic analgesics, anticonvulsants, psychotropics ) Depression Anxiety and agitation Vit D def Malnutrition Poor balance Weak muscles Kyphosis Reduced proprioception 25 26 WHO definition of osteoporosis WHO Definition BMD T score BMD T score >2.5SD at or below -2.5 1-2.5SD Between -1 and -2.5 Below the mean peak adult Below the mean peak adult Osteoporosis Osteopenia Although these definition are necessary to establish the presence of osteoporosis, they should not be used as sole determinant of treatment decisions BMD T score <1SD At -1.0 and above Below the mean peak adult Normal 28
Bone Densitometry Dual x-ray absorptiometry (DXA) Quantitative computed tomography (QCT) mainly use in research field Quantitative ultrasound Dual x-ray absorptiometry (DXA) Measure the BMD of lumbar spine ( L1-L4) and the hip ( femoral neck and total hip ) Diagnosis based on T-score ( WHO definition of osteoporosis ) 29 30 32
Quantitative Ultrasound (QUS ) Can only used on peripheral bones e.g heel Advantages of small size, relatively quick and simple measurements, and no radiation 33 34 Indications for BMD testing ( NOF recommendation ) Women > 65 and men > 70, regardless of clinical risk factors Younger postmenopausal women and men age 50-70 about whom you have concern based on their clinical risk factor profile Women in the menopausal transition if there is a specific risk factor associated with increased fracture risk such as low body weight, prior low trauma fracture, or high risk medication 36
Indications for BMD testing ( NOF recommendation ) Adults with a condition (e.g RA ) or taking a medication (e.g, steroid >5mg/day for > 3months) associated with low bone mass or bone loss Anyone being considered for pharmacologic therapy for osteoporosis Anyone being treated for osteoporosis, to monitor treatment effect Management ***Multidisciplinary approach 37 38 Universial Recommendations 1. Adequate intake of calcium and Vit D 2. Regular weight bearing exercise 3. Fall prevention 4. Avoidance of tobacco use and excessive alcohol intake Adequate intake of calcium and vitamin D Lifelong adequate calcium intake is necessary for the acquisition of peak bone mass and subsequent maintenance of bone health NOF recommend 1200mg for women age over 50 39 40
Adequate intake of calcium and vitamin D Vitamin D plays a major role in calcium absorption, bone health, muscle performance, balance, and risk of falling NOF recommends an intake of 800 to 1000 IU of vitamin D3 ( cholecalciferol ) per day for adults over age 50 Drug Treatment 41 42 NOF Guideline Who Should Be Treated??? Postmenopausal women and men age 50 and older presenting with the following should be treated : A hip or vertebral fracture Other prior fracture and low bone mass T score <2.5 at the femoral neck, total hip or lumbar spine after appropriate evaluation to exclude secondary causes 43 44
NOF Guideline Antiresorptive agents Low bone mass with secondary causes associated with high risk of fracture ( such as steroid use or total immobilization ) Low bone mass and 10-yr probability of hip fracture >3% or a 10-yr probability of any major osteoporosis related fracture >20% based on the WHO model 45 Bisphosphonates - Alendronate - Risedronate - Ibandronate ( oral and IV ) - Zoledronate (IV) Selective Estrogen Receptor Modulators (SERM) - Raloxifene Strontium * ( dual action ) Calcitonin HRT 46 Anabolic agent Bisphosphonate PTH 1-34 ( Parathyroid hormone ) Inhibitors of osteoclast activity Strong affinity for calcium ions and are rapidly taken up by bone Long skeletal half life??? Long term side effects over suppressed bone turnover 47 48
Alendronate ( Fosamax ) 70mg oral weekly New formulation ( fosamax plus ) had vitamin D3 2800/5600IU Reduce vertebral fracture by 48% over 3 years in patient w/o prior vertebral fracture Reduce the incidence of vertebral and nonvertebral fracture by around 50% in patient with prior vertebral fracture Ibandronate ( Bonviva ) 150mg oral once a month 3mg every 3 months by IV injection Reduces the incidence of vertebral fracture by about 50% over 3 years 49 50 Risedronate ( Actonel ) 35 mg oral weekly Reduces the incidence of vertebral fracture by 41-49% and non-vertebral fracture by 36% over 3 years Zoledronate ( Aclasta ) 5mg by IV infusion over at least 15 mins once yearly Reduces the incidence of vertebral fracture by 70%, hip fracture 41% and non-vertebral fracture by 25% over 3 years 51 52
Side effects of Bisphosphonates Similar for all oral bisphosphonates which include GI problems such as dyspepsia, nausea, pain in the bones, muscles and joints. ( need to be taken on an empty stomach, 1st thing in the morning with plenty of plain water, at least 30-60 mins before eating or drinking, remain upright during this interval as well ) Side effects of Bisphosphonates Osteonecrosis of the jaw have been reported (very rare in osteoporosis cases) - usually seen in oncology cases with high dose IV bisphosphonate 53 54 Drug Interactions with bisphosphonate No clinical significant interactions with most common medications SERM (Selective Estrogen Receptor Modulator) Raloxifene ( Evista ) 60mg oral daily Reduces the risk of vertebral fracture by 55% in patients with prior fracture, 30% in patients w/o prior fracture over 3 years Reduces the risk of breast cancer Increase risk of DVT Increase hot flashes 55 56
Effect of Raloxifene on All Breast Cancer Incidence MORE Trial - 4 Years % of Randomized Patients 2.0 1.5 1.0 0.5 RR = 0.38 (95% CI = 0.24-0.58) NNT = 94 * 0.0 0 1 2 3 4 Years since Randomization 62% Placebo RLX (pooled) Arrow denotes annual mammogram (*optional) Total Cases = 77 Adapted from Cauley J et al. Breast Cancer Res Treatment 65:125-34, 2001 57 Strontium Ranelate ( Protos ) Both anti-resorptive and anabolic effects 1 sachet ( 2 g ) daily to be taken at bedtime Reduces vertebral fracture risk by 41% in 3 years, non-vertebral fracture risk by 16% Side effects of nausea, diarrhea, headache, skin irritation Risk of DVT may be increased 58 Calcitonin Salmon calcitonin Single daily intranasal spray / s.c inj No big RCT data to look at fracture risk reduction May reduce back pain caused by acute vertebral fracture S/E of nausea, vomiting, dizziness and flushing may occur 59 HRT ( Hormone Replacement Therapy ) Reduces the risk of clinical vertebral fracture and hip fracture by 34% and other osteoporotic fracture by 23% over 5 years Increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli and DVT during the 5 years of treatment No longer used as 1st line agent to treat osteoporosis 60
Anabolic agent PTH 1-34 ( Forteo ) Daily s.c injection Reduces the risk of vertebral fracture by 65% and non-vertebral fracture by 53% in patients with osteoporosis, after an average use of 18 months PTH 1-34 (Forteo) Side effects of leg cramps and dizziness Relatively expensive Safety and efficacy has not been demonstrated beyond 2 years of treatment Common practice to follow PTH treatment with an anti-resorptive agent 61 62 Combination therapy?? Remaining issues Not recommended no good research evidence to show better fracture outcome 63 64
How can we better assess bone strength using non-invasive technologies and thus improve identification of patients at high risk of fracture? How effective are different drug treatments in preventing fractures in patients with moderately low bone mass? How long should anti-resorptive therapies be continued, and are there long term side effects as yet unknown? Are combination therapies useful, and if so, which are the useful drug combinations and when should they be used? Can we identify agents that will significantly increase bone mass and return bone structure to normal Summary 65 66 Osteoporosis Global public health problem Very common condition among elderly ( 1 in 2 for women and 1 in 5 in men ) Fracture can KILL Can be easily diagnosed and have very effective drug treatment Multidisciplinary approach 67 68