New Trends in Management of Osteoporosis

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Slide 1: 

بسم الله الرحمن الرحيم

Dr. Hany Zahran : 

Dr. Hany Zahran Cons. Rheumatology & Rehabilitation Al Pasha Medical CenterM.D., Rh. & Rehab., Kasr El Eini, Cairo University Fellow & member of ACR Fellow of ILAR, EULAR & APLAR Head of dept. of Rheum.& Rehab., university of 6th Oct. H. Medical Consultant for Ahli club & EHF, A.R.E. Presents…

New Trends In management of osteoporosis : 

New Trends In management of osteoporosis

Slide 4: 

New defintion Bone Strength replacing BMD as the key endpoint for proof of efficacy Definition of Osteoporosis “Osteoporosis is a skeletal disorder characterized by compromised bone strength predisposing a person to an increased risk of fracture.”1 Normal Osteoporosis 1. Consenses Development Conference, JAMA 2001; 285: 785-95. 1993 consensus conference “osteoporosis is a systemic skeletal disease characterized by low bone mass and micro-architectural deterioration of bone tissue with a resultant increase in fragility and risk of fracture

Slide 5: 

5 THE SIZE OF THE PROBLEM

Slide 6: 

6 INCIDENCE (Epidemiology) Incidence is difficult to measure, as most cases a are not recorded until a fracture has occurred. The National Osteoporosis Society (UK) stated that at least 1 in 3 women and 1 in 12 men will develop osteoporosis 28 million in US 3 out of 10 women above 50 Hereditary Factors Gender. Race.

Osteoporosis is a Prevalent Disease : 

7 Osteoporosis is a Prevalent Disease Affects 200 million women worldwide1 - 1/3 of women aged 60 to 70 - 2/3 of women aged 80 or older Approximately 20-25% of women over the age of 50 have one or more vertebral fractures2 - United States: 25%3 - Australia: 20%4 - Western Europe: 19 % - Scandinavia: 26%5 - Denmark: 21%6 1. International Osteoporosis Foundation 4. Jones G et al., Osteoporos Int 1996, 6:233 2. Melton LJ 3rd et al., Spine 1997, 22:2S 5. O'Neill et al., J Bone Miner Res 1996, 11:1010 3. Ettinger B et al., J Bone Miner Res 1992,7:449 6. Jensen GF et al., Clin Orthop 1982,166:75

Osteoporosis in Saudi Arabia : 

8 Osteoporosis in Saudi Arabia 50-59 yrs : 33.4% osteopenia 24.3% osteoporotic 60-69 yrs : 27% osteopenic 62% osteoporotic 70-80 yrs : 21.5 osteopenic 73.8 osteoporotic Osteoporosis in postmenopausal Saudi women using dual x-ray bone densitometry  .  Mahmoud I.  El-Desouki, SAUDI MEDICAL JOURNAL)

Osteoporotic Fractures in Women: Comparison with Other Diseases : 

9 Osteoporotic Fractures in Women: Comparison with Other Diseases Riggs BL, Melton LJ. Bone 1995 Heart and Stroke Facts, 1996, American Heart Association Cancer Facts & Figures, 1996, American Cancer Society

Some Costs of Osteoporosis in Europe : 

10 Some Costs of Osteoporosis in Europe In Europe the total direct costs of osteoporotic fractures are over €31 billion and are expected to increase to more that €76 billion in 2050. Kanis JA & Johnell O. - Osteoporos Int 2005 (in press) In France osteoporotic hip fractures are estimated to cost about €1 billion every year* In Spain the total direct hospital cost of osteoporotic fractures in 1995 was approximately €222 million* In England & Wales the total direct hospital cost of osteoporotic fractures in 1999 was approximately €847 million* *Osteoporosis in the European Community: A Call to Action. IOF Nov, 2001

Bone Strength : 

Bone Strength Bone Quality -Micro-Architecture Connectivity BTM Mineralization Micro-damage Collagen cross-linking Bone Quantity Mass Bone Mineral Density Size Bone Strength is the Function of Multiple Factors!

Slide 12: 

Determinants of the Antifracture Efficacy of an Osteoporosis Treatment Bone Mineral Density + Bone Turnover + Micro architecture = Bone Strength

Slide 13: 

Clinical Picture Not all fractures come to physician attention “Two Third of Vert Fracture did not come to physician attention” Patient has to lose > 30 % of Bone Mass to be diagnosed by X ray Silent Thief

Slide 14: 

Spinal Deformity & Height Loss

Slide 15: 

Goals of Osteoporosis Therapy Prevent fractures Stabilize or improve bone mass Minimize symptoms Improve physical function Enhance patient’s quality of life

Slide 16: 

Practical Problems frequently met with in diagnosis and treatment of osteoporosis and the basis of the most recent trends of their management

What Are They? : 

What Are They?

Slide 18: 

Prophylaxis of osteoporosis in menopausal women. To use HRT or not? Should women be screened with DEXA? Osteoporosis and corticosteroid therapy in the postmenopausal female with rheumatoid arthritis. Osteoporosis in the male. The management of hip fractures in the elderly. Pain caused by stress or insufficiency fractures. Fracture of the axial skeleton: osteoporotic or neoplastic? Rehabilitation of the severely disabled elderly osteoporotic woman.

Slide 19: 

Prophylaxis of osteoporosis in menopausal women – to use HRT or not? Should women be screened with DEXA?

Definition Of The Problem : 

Definition Of The Problem Osteoporosis is a disease predominantly affecting postmenopausal women. A 50 years old white woman has a 40% lifetime risk of any hip, vertebral or distal forearm fracture, whereas in men this risk is 13%.

Slide 21: 

Hormone replacement therapy (HRT) prevents bone loss and fracture in postmenopausal women. Oestrogen also improves quality of life by alleviating menopausal symptoms and reducing risk of coronary heart disease and stroke. Despite this, the uptake of and compliance with HRT is low.

Slide 22: 

Bone density measured by DEXA is the best predictor of fracture risk. How should HRT be used to prevent osteoporosis and what is the role of bone densitometry in identifying whom to treat?

Therapeutic options : 

Therapeutic options Osteoporosis is prevented by maximizing and maintaining bone mass and preventing trauma. Bone mass is influenced by dietary calcium, vitamin D, physical activity, smoking and excess alcohol. Lifestyle changes can be used to maximize it, but their effectiveness is limited.

Slide 24: 

A rapid phase of bone loss is associated with the menopause and HRT has been shown to prevent bone loss in prospective controlled clinical trials. Case-control retrospective cohort studies and a limited number of prospective studies show a reduction in fracture risk of variously, the hip, spine and forearm with long term use of HRT.

Slide 25: 

The benefit is considerable, with most studies showing a reduction in risk of hip fracture of 50-75% in oestrogen users. The minimum duration for significant reduction in fracture risk is 5 years. The benefit is greatest in long-term recent users, that is, those using HRT close to the expected age of fracture.

Slide 26: 

Bone loss is most rapid close to the menopause therefore, initiation close to the menopause and for as long as possible is ideal. Long-term oestrogen therapy is also associated with a reduction in cardiovascular disease.

Slide 27: 

The principle limitation to the effectiveness of HRT in preventing osteoporosis and fracture is the poor uptake and long-term compliance. So, how can this be improved? 1- public education of the risks of osteoporosis and benefits of HRT. 2- Identifying those who will gain most those at highest risk.

Bone density measured by x-ray absorptiometry : 

Bone density measured by x-ray absorptiometry Is the best predictor of future fracture risk available at present.

Slide 29: 

Although there are clinical risk factors for osteoporosis e.g. smoking, excess alcohol and low body weight, they lack specificity and only predict 30% of bone mass at best and can’t be used for clinical decision making.

Slide 30: 

Bone density measured by DEXA correlates with bone strength, and for each standard deviation fall in bone density, the relative risk of fracture doubles.

Slide 31: 

Prevention in a population is at present a combination of these approaches: 1- improving lifestyles. 2- encouraging the use of effective means of prevention HRT, in particular for high risk cases.

Slide 32: 

The most effective means of prevention for an individual is HRT. It should be started close to the menopause and taken for at least 5 years.

Slide 33: 

Bone mineral density is the best way for an individual to know their future risk of fracture and enables them to act upon it. Knowledge of bone density has been shown to increase uptake of and compliance with HRT.

Slide 34: 

Measurement is indicated, therefore if it will play a role in clinical decision making for example among asymptomatic individuals with a variety of conditions that predispose them to osteoporosis these includes: 1-an early menopause. 2-prolonged amenorrhea. 3-long-term corticosteroids. 4-hypogonadism. 5-anorexia nervosa. 6-Alcohol abuse. 7-thyrotoxicosis. 8-Rheumatoid arthritis .

Slide 35: 

Osteoporosis & Corticosteroid therapy in the postmenopausal female with rheumatoid arthritis

Definition of the problem : 

Definition of the problem Osteoporosis is a well recognized complication of R.A. In addition to juxta-articular osteoporosis, a generalized osteoporosis is commonly observed and postmenopausal women appear to be most at risk of exhibiting this generalized bone loss.

Slide 37: 

Low-dose corticosteroids are commonly used as adjunctive therapy for disease control in R.A. Corticosteroid in high doses are associated with accelerated bone loss. Whether low doses increase generalized osteoporosis in RA remains of concern to rheumatologists (clinicians).

Management : 

Management When it is necessary to use corticosteroids, employ the lowest dose possible for the shortest duration possible. Monitor bone density to assess fracture risk Use calcium supplements (500-1000mg/day). Use cyclical estrogen replacement therapy in postmenopausal women. Consider calcitriol or a biphosphonate in patients starting higher doses >7.5mg/day.

Osteoporosis in the male : 

Osteoporosis in the male

Definition of the problem : 

Definition of the problem Osteoporosis fragility fractures affect mainly postmenopausal women. However, the problem is far from uncommon in middle aged and elderly men. Vertebral fractures occur in about 36/100,000 patient years. The lifetime risk for femoral neck fractures is 5%, compared with 12% in women. In men, secondary osteoporosis is more common than in women.

Therapeutic options : 

Therapeutic options When a patient presents with secondary osteoporosis: Any underlying disease should be treated. Furthermore, when possible prevention of further bone loss should be considered before fracture occur.

Slide 44: 

When fractures have occurred pain can be suppressed by: Rest. Analgesics. Calcitonin.

Slide 45: 

Risk factors (e.g. smoking, alcohol intake and immobilization) should be avoided. Calcium intake should be at least 1500mg/day provided by milk products or calcium supplements, with at least one intake in the evening. Vit. D supplements: sun exposure or when necessary 400-800 IU/day. Physical exercise e.g. walking should be encouraged, although care must be taken to avoid falls.

In corticosteroid induced osteoporosis: : 

In corticosteroid induced osteoporosis: Calcium supplements. Pharmacologic dose of vit. D. Anabolic steroids when serum .testosterone is low and muscle wasting is prominent. Changes in the corticosteroid preparation and its dose, and the combination medication that inhibit bone resorption or stimulates bone formation should be considered.

Slide 47: 

When hypogonadism is present: testosterone substitution therapy should be started. Incase of hypercalciuria: Thiazides. When no underlying disease is found: Adequate calcium. Vitamin D.

Slide 48: 

Inhibition of bone resorption by: Calcitonin: indicated when pain. Bisphosphonates. Sodium fluoride can be considered when trabecular bone is decreased in the presence of sufficient amounts of cortical bone.

Slide 49: 

Anabolic steroids are indicated when serum testosterone is low and muscle wasting is prominent.

The management of hip fractures in the elderly : 

The management of hip fractures in the elderly

Definition of the problem : 

Definition of the problem Hip fractures are a common problem in elderly people. In these elderly people, not only the quality of bone but also neurological and cognitive factors influence the number of hip fractures that may result from a trivial trauma. The quality of the bone may be diminished by a loss in total mass of bone (osteoporosis) or by a deficiency in the mineralization of bone (osteomalacia).

Pain caused by stress or insufficiency fractures : 

Pain caused by stress or insufficiency fractures

Definition of the problem : 

Definition of the problem Stress or insuffiency fracture develops without any specific episode of trauma. They occur in individuals with other musculo-skeletal disorders, but they also occur in individuals with no history of injury or disease.

Slide 56: 

Plain radiographs may demonstrate changes consistent with a fracture, including a fracture line or fracture callus, but in many cases radiographs will be normal or non diagnosed. In these instances a bone scan, CT or MRI will usually demonstrate abnormalities consistent with a fracture.

Therapeutic options : 

Therapeutic options Stress fracture generally heal spontaneously but occasionally they displace. Some patients have developed persistent or recurrent stress fractures. Most patients can be treated with: Activity modification. external support. Analgesics. Some require surgical stabilization to prevent displacement or stimulate healing.

Fracture of the axial skeleton osteoporotic or neoplastic? : 

Fracture of the axial skeleton osteoporotic or neoplastic?

Slide 62: 

Homogenous replacement of vertebral signal in a patient with a known primary carcinoma is a strong indication of pathologic fracture rather than benign insufficiency fracture. Osteoporotic fractures typically produce heterogeneous marrow changes.

Rehabilitation of the severely disabled elderly osteoporotic woman : 

Rehabilitation of the severely disabled elderly osteoporotic woman

Therapeutic options : 

A multidisciplinary approach is necessary including: Medical. Nursing. Physical therapy. Occupational therapy. Social worker input. Therapeutic options

Slide 67: 

The main goal is to re-establish the independence of the patient and early mobilization should be attempted to avoid pressure sores, conditions, disorientation and thromboembolism. Detailed review of the patients medication and its rationalization.

Slide 68: 

Adequate analysis is appropriate for back pain but tranquilizers or sedatives should be avoided. If back pain is persistent, bone scintigraphy may be useful to identify the origin of the pain is in the vertebral bodies or apophygeal joints (for the latter, specific treatment may be helpful).

Slide 69: 

Back braces should generally be avoided as they weaken back extensor muscle strength, but may occasionally be necessary in patients with sever kyphosis (CASH ORTHOSIS).

Slide 70: 

Specific treatment of osteoporosis in the elderly is associated with a greater likelihood of adverse reactions to medication, but there is increasing evidence that it is a cost effective way of preventing further fractures: Ca supplement if dietary Ca intake is adequate. Vitamin D supplement if vit. D is deficient. Oestrogen occasionally, but be commenced gradually with initial low doses. Anabolic steroids can be used for shorter periods in older patients who are catabolic. Exercise programs may be most useful in relation to preventing further falls.

Slide 71: 

Special rehabilitation: Improve coordination. Gradual strengthening of muscle power. Ensure that the home environment is safe. A variety of aids for promotion of independent living.

OVERVIEW OF INTERNATIONAL CURRENTLY USED GUIDELINES FOR PREDICTION, DIAGNOSIS AND TREATMENT OF OESTEOPROSIS : 

OVERVIEW OF INTERNATIONAL CURRENTLY USED GUIDELINES FOR PREDICTION, DIAGNOSIS AND TREATMENT OF OESTEOPROSIS

Slide 73: 

Rapid Risk Assessment BMD Measurement BMD Measurement BMD Measurement No Adapted from: National Osteoporosis Foundation. Physician’s Guide to Prevention and Treatment of Osteoporosis. 1998.

Slide 74: 

NOF/WHO Criteria for Assessing Disease Severity Normal >-1.0 Osteopenia Between-1.0 To – 2.5 (low bone mass) Osteoporosis £ -2.5 Severe (established) osteoporosis £ -2.5 with fracture T-score Bone mass score: The standard deviation in a patient’s bone mineral density (BMD) compared with the peak bone mass in a young adult of the same gender World Health Organization (WHO) National Osteoporosis Foundati on (NOF) Physicians Guide to Prevention & Treatment of Osteoporosis, 1998

Slide 75: 

Staging of osteoporosis based on BMD (DEXA) and vertebral fracture Clinical Stage osteopenia (preclinical osteoporosis) Osteoporosis without fractures Established osteoporosis (with fractures) Advanced osteoporosis Criteria lowered BMD (T score: 1 to 2.5 SD) reduced BMD, no fractures (T score: <—2.5 SD) reduced BMD -trauma, vertebral fractures ( T score : > —2.5 ) - reduced BMD, multiple vertebral fractures, often non-vertebral fractures

Slide 76: 

Preferred BMD Measurement Technologies Dual-energy x-ray absorptiometry (DEXA) Lumbar spine Proximal femur Quantitative computed tomography (QCT) Spine Forearm Peripheral DEXA Forearm

Rapid Treatment Decision : 

T-score below -2.0? Rapid Treatment Decision Adapted from: National Osteoporosis Foundation. Physician’s Guide to Prevention and Treatment of Osteoporosis. 1998. Treat all patients with an existing fracture! Check patient in 1-2 years Treat if other risk factors present Treat patient

Slide 78: 

2002 clinical practice guidelines for the diagnosis and management of osteoporosis in Canada Jacques P. Brown, Robert G. Josse and The Scientific Advisory Council of the Osteoporosis Society of Canada CMAJ.NOV.12,2002

Slide 79: 

Who Should be tested for osteoporosis?

Slide 80: 

Who Should undergo a fracture risk assessment and be treated for osteoporosis? Long - term glucocorticoid therapy Personal history of fragility fracture after age 40 Non-traumatic vertebral compression deformities Clinical risk factor (1 major or 2 minor) Low BMD by DXA (T-score below - 2.5) AND LOW BMD by DXA (T-score below - 1.5 ) Start Bisphosphonate therapy Consider therapy Repeat BMD by DXA after 1 or 2 year Obtain BMD by DXA for follow-up CMAJ.NOV.12,2002;167( 10 supp) 2002 Canadian Osteoporosis Guideline

Fracture Recognition : 

Established osteoporosis may still be recognized on radiographs of the spine. However, because some two-thirds of spinal fractures are not diagnosed clinically, one cannot rely on radiographs obtained to investigate back pain. CMAJ.NOV.12,2002;167( 10 supp) 2002 Canadian Osteoporosis Guideline Fracture Recognition

Definitions : 

The World Health Organization (WHO) defines fragility fracture as “A Fracture caused by injury that would be insufficient to fracture normal bone: the result of reduced compressive and/or torsional strength of bone.” Cont. Fragility Fracture CMAJ.NOV.12,2002;167( 10 supp) 2002 Canadian Osteoporosis Guideline Definitions

Osteoporotic Vertebral Fracture : 

Measurements of the vertical height of a vertebra at its anterior margin, center (or mid-position) and posterior margin on lateral spine radiographs. If these measurements differ from each other or from the same measurements in the supra or sub-adjacent vertebrae by 20% or more CMAJ.NOV.12,2002;167( 10 supp) 2002 Canadian Osteoporosis Guideline Osteoporotic Vertebral Fracture

Discussions Rare : 

Discussions Rare 1 in 3 physicians discussed osteoporosis with female patients <50% of physicians discussed the importance of calcium with their patients 3 of 4 women never talked with their physicians about osteoporosis 40% of women saw no need to discuss osteoporosis McKinney M. Medical Tribune. 1998.

Insufficient Diagnosis and Treatment : 

Insufficient Diagnosis and Treatment Early detection is essential for prevention Risk of fracture increases with age Risk of fracture increases with each subsequent fracture Even small increases in BMD can substantially reduce the risk of fracture Wrist fracture is a strong predictor of hip fracture, especially among older women It is never too soon or too late to treat

Therapeutic options for osteoporosis : 

Therapeutic options for osteoporosis Combined therapies Osteoanabolic treatment PTH Anti resorptive treatment BP, SERM, CCt, Exercise, fall prevention Basic treatment RF-assessment and advice; Ca/D3-supplementation

Pharmacological Therapy of Postmenopausal Osteoporosis : 

Prevention Treatment       Pharmacological Therapy of Postmenopausal Osteoporosis HRT Various SERM -Raloxifene (Evista®) Bisphosphonates Etidronate (Didronel®)* Alendronate (Fosamax®) Risedronate (Actonel®) Ibandronate (Boneviva) Zoledronic acid 5mg (ACLASTA®) Calcitonin Calcitonin (Miacalcic®)      

International Osteoporosis Foundation Journal : 

International Osteoporosis Foundation Journal A consensus document developed by IOF members together with Belgium Bone Society. Published in March 2005

Slide 89: 

There is no linear relationship between increases in BMD and fracture risk reductions. Different anti-resorptives should not be compared on the basis of their respective impact on BMD. Combination use of anti-resorptive agents cannot be recommended. Current data discourage the concomitant use of Alendronate and Teriparatide since the bisphosphonates appears to blunt the anabolic action of the Teriparatide.

BMD increase is not proportional to reduction of relative risk of vertebral fracture : 

BMD increase is not proportional to reduction of relative risk of vertebral fracture

Calcitonin : 

Analgesic properties maybe an interesting option for acute pain following a spinal fracture. Main drawbacks is its high cost. Calcitonin

MOST RECENT FDA APPROVED ONCE YEARLY ANTIRESOPTIVE (ANTIFRACTURE) BONE AGENT FOR PMO : 

MOST RECENT FDA APPROVED ONCE YEARLY ANTIRESOPTIVE (ANTIFRACTURE) BONE AGENT FOR PMO

Zoledronic acid 5mg (Aclasta) : 

Zoledronic acid 5mg (Aclasta) Zoledronic acid is a potent nitrogen–containing bisphosphonate - Core bisphosphonate moiety (red arrows) - R2 side chain: imidazole ring (blue arrows)

Conclusion : 

94 Conclusion Aclasta 5mg is likely to prevent more real-life fractures than other anti-resorptives with an acceptable impact on healthcare system budgets Only once-yearly Aclasta 5mg guarantees patient compliance for a full year in a single dose and assures 365 days of bone protection Only Aclasta 5mg is proven to prevent fractures at all of the most critical sites (hip, spine and nonspine) Excellent efficacy: an annual dose of Aclasta 5mg provided a 70% reduction in new vertebral fractures over 3 years Sustained efficacy: Aclasta 5mg is the only bisphosphonate proven to sustain the same level of fracture protection from Year 2 to Year 3 of treatment (from 71% to 70%) Aclasta 5mg reduces days of disability due to fracture and due to back pain (p<0.01)

Conclusion : 

95 Conclusion Aclasta 5mg has the FDA & European Union approval for postmenopausal osteoporosis Aclasta 5mg is Reducing mortality after hip surgical screw or replacement Aclasta 5mg is Registered in KSA MOH for treatemnt of postmenopausal osteoporosis & Paget’s disease of bone Aclasta 5mg has high safety & tolerability profile Aclasta 5mg is easily administered through 15 minutes infusion once yearly.

Slide 96: 

THANK YOU

Slide 97: 

Normal bone Osteoporosis Osteoporosis is defined as a skeletal disorder characterized by compromised bone strength predisposing a person to an increased risk of fracture. Current Definition of Osteoporosis NIH Consensus Development Panel on Osteoporosis. JAMA 285 (2001): 785-95

Slide 98: 

[SP0034] COMBINATION THERAPIES IN OSTEOPOROSIS W.F. Lems. Rheumatology, Vrije Universiteit Medical Centre, Amsterdam, Netherlands Since osteoporotic patients are at high risk for fractures, the goal of anti-osteoporotic therapy is reduction of fracture risk. Nowadays, several anti-osteoporotic drugs are available: antiresorptive drugs (bisphosphonates, selective estrogen receptor modulators), and anabolic agents (PTH 1-34, teriparatide, and PTH 1-84). It is remarkable that both the antiresorptive drugs and the anabolic agents have been shown to be effective in the prevention of vertebral fractures in osteoporotic patients, while some of these drugs have also shown a reduction in nonvertebral- and hip fractures. In the treatment of severe osteoporotic patients with a high fracture risk, e.g. an elderly woman with a low T-score, vertebral deformities and a nonvertebral fracture, the question arises whether the use of combination therapy with a bisphosphonate and PTH would provide a therapeutic advantage by combining different mechanisms for the reduction of fracture risk. Combination therapy, the simultaneous use of two pharmaceutical agents with the goal to reduce the fracture risk, is an area of substantial clinical interest [1]. The most important question is, are there any data showing that combination therapy in osteoporotic patients improves efficacy by a further reduction in fracture rate (versus monotherapy)? Unfortunately, since we do not have such data, combination therapy cannot be recommended in daily practice. What about surrogate markers, such as changes in BMD and markers of bone turnover? In small studies, combination of 2 different antiresorptives (eg, raloxifen plus bisphosphonates) produce greater increases in bone mineral density than either treatment alone. However, since we have strong arguments that antifracture efficacy derives from other effects than changes in BMD, these data are very difficult to interprete, and translation to daily practice seems to be impossible. On the other hand, in 2 studies, both in men and in postmenopausal women, the combination of anabolic agents (PTH 1-34 or PTH 1-84) with alendronate has no additive effects on the changes in BMD, probably because these drugs are counteracting: the expected large and sustained increases in bone formation were not observed during the entire study period of 1 year in the patients with combination therapy [2,3]. The other clinically relevant issue is about sequential therapies: the increases in BMD of the spine and hip, induced by the use of parathyroid hormone, are rapidly lost after treatment discontinuation, but preserved when bisphosphonates are given as sequential therapy [4,5]. In summary, the currently available literature do not support the combined use of antiresorptives and anabolics, while the data suggest that after initiating a treatment with an anabolic agent, it may be necessary to maintain the effect with an antiresorptive agent. References: 1. Heaney RP, Recker RR. Combination and sequential therapies for osteoporosis. New Engl J Med 2005; 353: 624-5. 2. Finkelstein J, et al. The effects of parathyroid hormone, alendronate, or both in men with osteoporosis. New Engl J Med 2003; 1349: 216-26. 3. Black DM, et al. The effects of parathyroid hormone and alendronate alone or in combination in postmenopausal osteoporosis. New Engl J Med 2003; 349: 1207-1215. 4. Black D, et al. One year of alendronate after one year of parathyroid hormone (1-84) for osteoporosis. New Engl J Med 2005; 353: 555-65. 5. Kaufman JM, et al. Teriparatide effects on vertebral fractures and BMD in men with osteoprosis: treatment discontinuation of therapy. Osteoporis Int 2005; 16: 510-6. Citation: Ann Rheum Dis 2006;65(Suppl II):14 Date: Thursday, June 22, 2006 Session Info: Osteoporosis Close Window

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[FRI0428] OSTEOPOROSIS ACCELERATES CARTILAGE DAMAGE IN A RABBIT EXPERIMENTAL MODEL OF OSTEOARTHRITIS S. Castañeda1, R. Largo 2 , E. Calvo 3 , F. Rodriguez-Salvanes 1 , G. Herrero-Beaumont 2. 1Rheumatology, Hospital de la Princesa, 2Rheumatology, 3Orthopaedic Surgery, Fundacion Jimenez Diaz, Madrid, Spain Background: The relationship between osteoporosis (OP) and osteoarthritis (OA) is not well established. Although some authors support an inverse relationship between them, other studies suggest that OP could increase the progression of OA. Objectives: To evaluate the influence of OP on the cartilage damage in an experimental model of OA in rabbits. Methods: Experimental OA was induced in 11 female NZ white rabbits (10 months old; 4.2 0.4 kg body weight) by anterior cruciate ligament section and medial meniscectomy (ACL+M) in the left knee. OP was previously induced in 6 rabbits by ooforectomy (Ovx) and methylprednisolone (i.m.) administration (0.75 mg/kg/d for 5 wks) (OP+OA group). Bone mass was analyzed by dual energy X-ray absorptiometry (DXA) at baseline and 6 wks after Ovx (Hologic QDR-1000) in lumbar spine (L3-L4, LS) and subchondral bone of the knee (sK). Contralateral knees were used as healthy controls in the OA group, and OP knees in the OP+OA group. An experimental magnetic resonance image (MRI, 4.2 T) of the knee previous to surgery was obtained to evaluate baseline cartilage status. Animals were sacrificed 20 wks after ACL+M. A semiquantitative scale for macroscopic cartilage analysis and the Mankin s scale for the microscopic analysis were used. The effect of the different interventions was studied by ANOVA test of repeated measures. The correlation between bone mineral density (BMD) and histological damage was studied by Pearson s test (SPSS 10.0). Results: Baseline BMD values (mean±SD) at LS and sK were: 0.291±0.018 and 0.440±0.022, respectively in OP+OA group, and 0.310±0.027 and 0.477±0.036 mg/cm2, respectively in the OA group. Six weeks after Ovx, BMD values at LS and sK were 0.233±0.039 and 0.363±0.086, respectively, in OP+OA group, and 0.303±0.012 and 0.479±0.031 mg/cm2, respectively in the OA group (p < 0.05). Cartilage thickness measured by MRI previous to ACL+M did not show significant differences between healthy and pathological rabbits. Macroscopic and microscopic findings at sacrifice are shown in the table (Mean±SD). When microscopic findings were analyzed separately, a statistically significant difference in the histopathological lesions between OP+OA rabbits and the rest of the groups was observed (p< 0.01). Furthermore, an inverse correlation between microscopic damage and BMD was found (r=0.75 at LS; r=0.55 at sK). Macro and microscopical results Group (number of Knees) Control (n=5) OP (n=6) OA (n=5) OP + OA (n=6) Macroscopic scale 0.0±0.0 0.0±0.0 7.5±2.1* 8.0±3.3* Microscopic scale 0.2±0.4 2.0±1.0 3.5±2.6 9.0±3.1** p<0.01 vs. OP and Control: **p<0.01 vs. OP, OA and Control Conclusion: In our model, OP+OA rabbits showed an increase in the cartilage damage in comparison with OA non-osteoporotic rabbits. These results support recent clinical epidemiological findings suggesting that OP could be a risk factor for OA progression. Citation: Ann Rheum Dis 2006;65(Suppl II):414 Date: Friday, June 23, 2006 Session Info: Osteoporosis Close Window

Slide 100: 

[FRI0436] GUIDLEINS FOR OSTEOPOROSIS DRUG THERAPY: VALIDITY OF A SELF ADMINISTERED QUESTIONNAIRE TO STRATIFY THE PATIENTS ACCORDING TO THEIR RISK FACTORSY.M. El Miedany1, S.S. Youssef 1 , A. Mehanna 2 , F. Meky 3. 1Rheumatology and Rehabilitation, 2Radiology, 3Community, Enviromental and Occupational Medicine, Ain Shams University, Cairo, EgyptBackground: Given the increased number of new agents licensed for the treatment of osteoporosis and the various combinations of patient characteristics confronting the clinician, it seems prudent to evaluate if the patient has any of the risk factors that might contraindicate or interact with a specific osteoporosis therapy. Screening the patients for such risk factors would enable the clinician to choose a treatment that offers the best combination of therapeutic efficacy, patient's safety and cost-effectiveness.Objectives: to develop a valid self-administered questionnaire to stratify patients who are due to start osteoporosis therapy with regard to their risk factors for the various treatment options in a prospective study.Methods: Development of Osteoporosis Therapy Risk Assessment Questionnaire (OTRAQ) followed 5 stages: 1. Identification of the osteoporosis therapy risk factors after reviewing the literature. 2. Item pool development: a list of the main risk factors was compiled. Rare or uncommon factors were excluded. 3. A questionnaire was developed. This was based on the idea that the questions should be straight forward and as clear as possible. 4. Pre-testing of the questionnaire. 5. Validation of the questionnaire by comparing the patients answers with their medical notes. The last prescription was reviewed to verify the current medications. Comprehensibility of the model was also assessed.Results: stages 1 and 2 identified 6 main risk factors that were chosen for the questionnaire. These risk factors can be stratified as: cardiovascular, upper GIT, Liver disease, kidney affection, metabolic bone disease and concomitant medications. Stage 3 led to the development of a 20 items questionnaire. Analysis of the answers provided by 124 patients, age range 58-92 years revealed that the mean time to answer the questionnaire was 60.07 + 0.362 seconds. The OTRAQ has shown a strong validity when compared to the patients' data record (range 0.89-0.96). All patients rated the questionnaire as easily comprehensible. Comprehensibility of the various questions ranged between 97.7% and 99.1% denoting that all the questions were well understood by the great majority of patients.Conclusion: OTRAQ is a valid instrument that can be self-administered to assess risk factors for various therapies among patients who are due to start osteoporosis treatment. The questionnaire is simple, quick and accurate and can be used in standard clinical practice. This patient index provided a quick guide to individualized decision making for this group of patients who are in need to osteoporosis therapy.Citation: Ann Rheum Dis 2006;65(Suppl II):417Date: Friday, June 23, 2006Session Info: Osteoporosis Close Window

Slide 101: 

[FRI0436] GUIDLEINS FOR OSTEOPOROSIS DRUG THERAPY: VALIDITY OF A SELF ADMINISTERED QUESTIONNAIRE TO STRATIFY THE PATIENTS ACCORDING TO THEIR RISK FACTORS Y.M. El Miedany1, S.S. Youssef 1 , A. Mehanna 2 , F. Meky 3. 1Rheumatology and Rehabilitation, 2Radiology, 3Community, Enviromental and Occupational Medicine, Ain Shams University, Cairo, Egypt Background: Given the increased number of new agents licensed for the treatment of osteoporosis and the various combinations of patient characteristics confronting the clinician, it seems prudent to evaluate if the patient has any of the risk factors that might contraindicate or interact with a specific osteoporosis therapy. Screening the patients for such risk factors would enable the clinician to choose a treatment that offers the best combination of therapeutic efficacy, patient's safety and cost-effectiveness. Objectives: to develop a valid self-administered questionnaire to stratify patients who are due to start osteoporosis therapy with regard to their risk factors for the various treatment options in a prospective study. Methods: Development of Osteoporosis Therapy Risk Assessment Questionnaire (OTRAQ) followed 5 stages: 1. Identification of the osteoporosis therapy risk factors after reviewing the literature. 2. Item pool development: a list of the main risk factors was compiled. Rare or uncommon factors were excluded. 3. A questionnaire was developed. This was based on the idea that the questions should be straight forward and as clear as possible. 4. Pre-testing of the questionnaire. 5. Validation of the questionnaire by comparing the patients answers with their medical notes. The last prescription was reviewed to verify the current medications. Comprehensibility of the model was also assessed. Results: stages 1 and 2 identified 6 main risk factors that were chosen for the questionnaire. These risk factors can be stratified as: cardiovascular, upper GIT, Liver disease, kidney affection, metabolic bone disease and concomitant medications. Stage 3 led to the development of a 20 items questionnaire. Analysis of the answers provided by 124 patients, age range 58-92 years revealed that the mean time to answer the questionnaire was 60.07 + 0.362 seconds. The OTRAQ has shown a strong validity when compared to the patients' data record (range 0.89-0.96). All patients rated the questionnaire as easily comprehensible. Comprehensibility of the various questions ranged between 97.7% and 99.1% denoting that all the questions were well understood by the great majority of patients. Conclusion: OTRAQ is a valid instrument that can be self-administered to assess risk factors for various therapies among patients who are due to start osteoporosis treatment. The questionnaire is simple, quick and accurate and can be used in standard clinical practice. This patient index provided a quick guide to individualized decision making for this group of patients who are in need to osteoporosis therapy. Citation: Ann Rheum Dis 2006;65(Suppl II):417 Date: Friday, June 23, 2006 Session Info: Osteoporosis Close Window

Combination Therapy In Osteoporosis : 

Combination Therapy In Osteoporosis [SP0034] COMBINATION THERAPIES IN OSTEOPOROSISW.F. Lems. Rheumatology, Vrije Universiteit Medical Centre, Amsterdam, NetherlandsSince osteoporotic patients are at high risk for fractures, the goal of anti-osteoporotic therapy is reduction of fracture risk. Nowadays, several anti-osteoporotic drugs are available: antiresorptive drugs (bisphosphonates, selective estrogen receptor modulators), and anabolic agents (PTH 1-34, teriparatide, and PTH 1-84). It is remarkable that both the antiresorptive drugs and the anabolic agents have been shown to be effective in the prevention of vertebral fractures in osteoporotic patients, while some of these drugs have also shown a reduction in nonvertebral- and hip fractures.In the treatment of severe osteoporotic patients with a high fracture risk, e.g. an elderly woman with a low T-score, vertebral deformities and a nonvertebral fracture, the question arises whether the use of combination therapy with a bisphosphonate and PTH would provide a therapeutic advantage by combining different mechanisms for the reduction of fracture risk. Combination therapy, the simultaneous use of two pharmaceutical agents with the goal to reduce the fracture risk, is an area of substantial clinical interest [1]. The most important question is, are there any data showing that combination therapy in osteoporotic patients improves efficacy by a further reduction in fracture rate (versus monotherapy)? Unfortunately, since we do not have such data, combination therapy cannot be recommended in daily practice.What about surrogate markers, such as changes in BMD and markers of bone turnover? In small studies, combination of 2 different antiresorptives (eg, raloxifen plus bisphosphonates) produce greater increases in bone mineral density than either treatment alone. However, since we have strong arguments that antifracture efficacy derives from other effects than changes in BMD, these data are very difficult to interprete, and translation to daily practice seems to be impossible.On the other hand, in 2 studies, both in men and in postmenopausal women, the combination of anabolic agents (PTH 1-34 or PTH 1-84) with alendronate has no additive effects on the changes in BMD, probably because these drugs are counteracting: the expected large and sustained increases in bone formation were not observed during the entire study period of 1 year in the patients with combination therapy [2,3].The other clinically relevant issue is about sequential therapies: the increases in BMD of the spine and hip, induced by the use of parathyroid hormone, are rapidly lost after treatment discontinuation, but preserved when bisphosphonates are given as sequential therapy [4,5].In summary, the currently available literature do not support the combined use of antiresorptives and anabolics, while the data suggest that after initiating a treatment with an anabolic agent, it may be necessary to maintain the effect with an antiresorptive agent.References: 1. Heaney RP, Recker RR. Combination and sequential therapies for osteoporosis. New Engl J Med 2005; 353: 624-5.2. Finkelstein J, et al. The effects of parathyroid hormone, alendronate, or both in men with osteoporosis. New Engl J Med 2003; 1349: 216-26.3. Black DM, et al. The effects of parathyroid hormone and alendronate alone or in combination in postmenopausal osteoporosis. New Engl J Med 2003; 349: 1207-1215.4. Black D, et al. One year of alendronate after one year of parathyroid hormone (1-84) for osteoporosis. New Engl J Med 2005; 353: 555-65.5. Kaufman JM, et al. Teriparatide effects on vertebral fractures and BMD in men with osteoprosis: treatment discontinuation of therapy. Osteoporis Int 2005; 16: 510-6.Citation: Ann Rheum Dis 2006;65(Suppl II):14Date: Thursday, June 22, 2006Session Info: Osteoporosis Close Window