Postmenopausal osteoporosis M.M.EMAM MD Rheumatologist SBMU

WHO criteria for osteoporosis Normal a value of Tscore >-1 Osteopenia a value of -1>Tscore>-2.5 Osteoporosis a value of T-score<-2.5 Severe Osteoporosis Osteoporosis + fragility fracture References: WHO 1994

T-Score Z-Score

TBS especially informative in : Hyperparathyroidism DM type 2 Osteoarthritis Clinical and subclinical hypercortisolism Lumbar spine TBS may be particularly helpful in type 2 diabetes where BMD measurements and FRAX without TBS input do not adequately capture diabetes-associated fracture risk

Osteoporosis Treatment :

Who should be treated? If threshold WHO criteria T<-2.5 =60% lost of osteoporotic fractures

Who should be treated? In Postmenopausal women and men age 50 and older T- score<-2.5 Fragility fracture(hip and spine) after age 50 Osteopenia when: 10-year overall major fracture risk > 20% or the 10-year hip fracture > 3% In 10 -20 % according to judgment of physician NOF's New Clinician's Guide to Prevention and Treatment of Osteoporosis., 2013

20% 3 %

The case represents a woman the original FRAX probabilities for major osteoporotic and hip fracture, respectively, were 16 and 5.9%. The probabilities after entering the TBS value of 1.08 are shown.

Basic therapy for osteoporosis : Calcium & Vit.D supplementation Counteract individual risk factors Recommendation for physical activity Prevention of falls Smoke & alcohol ceasation References: 1. Spector TD. Rheum Dis Clin North Am 16:513-537, 1990. 2. Alarcón GS. Rheum Dis Clin North Am 21:589-604, 1995. 3. Goronzy JJ, Weyand CM, in Klippel JH (ed), Primer on the Rheumatic Diseases. 11th ed. Atlanta, Ga: Arthritis Foundation, 1997, pp 155-161.

Basic therapy for osteoporosis : Calcium & Vit.D supplementation Recommendation for physical activity Prevention of falls Smoke & alcohol ceasation Counteract individual risk factors References: 1. Spector TD. Rheum Dis Clin North Am 16:513-537, 1990. 2. Alarcón GS. Rheum Dis Clin North Am 21:589-604, 1995. 3. Goronzy JJ, Weyand CM, in Klippel JH (ed), Primer on the Rheumatic Diseases. 11th ed. Atlanta, Ga: Arthritis Foundation, 1997, pp 155-161.

Risk Factors for Osteoporosis and Fracture Non-Modifiable Age Female sex Maternal family history of hip fracture Low birth weight Disease predisposing to osteoporosis Potentially Modifiable History of falls Body mass index Drug therapy (e.g. corticosteroid use, use of anti-convulsants) Primary or secondary amenorrhea Early menopause Smoking Excessive alcohol consumption Dietary calcium and vitamin D deficiency Risk factors taken from Jordan & Cooper Best Practice and Res Clin Rheumatol, 2002 Categorized by Eli Lilly & Co.

Basic therapy for osteoporosis : Calcium & Vit.D supplementation Counteract individual risk factors Prevention of falls Smoke & alcohol ceasation Recommendation for physical activity References: 1. Spector TD. Rheum Dis Clin North Am 16:513-537, 1990. 2. Alarcón GS. Rheum Dis Clin North Am 21:589-604, 1995. 3. Goronzy JJ, Weyand CM, in Klippel JH (ed), Primer on the Rheumatic Diseases. 11th ed. Atlanta, Ga: Arthritis Foundation, 1997, pp 155-161.

Exercises : At least 30 minute 3 times per week Any weight bearing exercises especially jogging accepted Can increase BMD & muscle strength & propensity to fall

Basic therapy for osteoporosis : Calcium & Vit.D supplementation Counteract individual risk factors Recommendation for physical activity Smoke & alcohol ceasation Prevention of falls References: 1. Spector TD. Rheum Dis Clin North Am 16:513-537, 1990. 2. Alarcón GS. Rheum Dis Clin North Am 21:589-604, 1995. 3. Goronzy JJ, Weyand CM, in Klippel JH (ed), Primer on the Rheumatic Diseases. 11th ed. Atlanta, Ga: Arthritis Foundation, 1997, pp 155-161.

Prevention of falls & complications : Correction of decreased visual acuity Reduction of drug consumption that altered wakefulness & balance Improve cardiac & neurologic function Improve muscle strength Improving home environment Wearing hip protectors References: 1. Spector TD. Rheum Dis Clin North Am 16:513-537, 1990. 2. Alarcón GS. Rheum Dis Clin North Am 21:589-604, 1995. 3. Goronzy JJ, Weyand CM, in Klippel JH (ed), Primer on the Rheumatic Diseases. 11th ed. Atlanta, Ga: Arthritis Foundation, 1997, pp 155-161.

Mechanism Of Treatment Resorption Formation Teriparatide Anabolic hormones Rocaltrol Statins Fluoride !??? Bisphosphonates Miacalcic EPT SERM Prolia Strontium ranelate

Mechanism of treatment Resorption Formation Teriparatide Anabolic hormones Rocaltrol statins Fluoride !??? Bisphosphonates Miacalcic EPT SERM Prolia Strontium ranelate

Bisphosphonates : First line treatment in postmenopausal ,steroid induced & men  Alendronate or FOZAMAX (10 mg/day or 70 mg once weekly) or risedronate or Actonel (5 mg/day, 35 mg once weekly, or 150 mg once monthly), and ibandronate or Bonviva (150 mg once monthly or 3 mg intravenously every three months) are effective for both the prevention and treatment of osteoporosis and  Zoledronic acid (ZA) or aclasta , 5 mg administered intravenously (IV) once yearly, is also effective for the treatment of osteoporosis Has good effect on spinal & hip BMD & fracture risk Low intestinal absorption(So use in fasting state) Recently Actonel SR available that can be use after breakfast

Mechanism Of Treatment Resorption Formation Teriparatide Anabolic hormones Rocaltrol Statins Fluoride !??? Bisphosphonates Miacalcic EPT SERM Prolia Strontium ranelate

Calcitonin A less popular choice for treatment of osteoporosis is nasal calcitonin 200 international units daily. modest effect on BMD and weak antifracture efficacy Don't use in first years of menopause and fast looser state and hip involvement Had some analgesic effect Long term use associated with an increase risk of some cancers

Mechanism Of Treatment Resorption Formation Teriparatide Anabolic hormones Rocaltrol Statins Fluoride !??? Bisphosphonates Miacalcic EPT SERM Prolia Strontium ranelate

Denosumab

Denosumab Denosumab is a humanized monoclonal antibody against RANKL that reduces osteoclastogenesis. In several trials, Denosumab reduces the incidence of vertebral fractures by about 68 percent, hip fractures by about 40 percent and non-vertebral fractures by about 20 percent over three years 60 mg subcutaneously every 6 months

Denosumab Drug safety Hypocalcemia. Hypocalcemia must be corrected before starting increased the risk of serious skin infections (cellulitis) and skin rash. ONJ both when used to treat osteoporosis and to treat patients with cancer, although it is much more common in the latter setting Atypical femur fractures

long-term extension(8 years ) trial with Denosumab Zoledronate extending to 9 years that were also presented at the ASBMR meeting did not show similar progressive improvements in bone density or declines in fracture rates Denosumab seems to exert superior effects in the long term compared with the bisphosphonates Also reported at the ASBMR meeting in a late-breaking poster were the 8-year results from FREEDOM, which included 1382 subjects in the long-term denosumab group, who have so far received a cumulative 8 years of treatment, and 1296 patients in the group that crossed over from placebo. long-term data on zoledronate extending to 9 years that were also presented at the ASBMR meeting did not show similar progressive improvements in bone density or declines in fracture rates, casting some doubt as to the role of a healthy cohor American Society for Bone and Mineral Research 2013 Annual Meeting. ; Abstract LB-MO26, presented October 7, 2013

Combined teriparatide and denosumab increased BMD more than either agent alone and more than has been reported with approved therapies. Combination treatment might, therefore, be useful to treat patients at high risk of fracture Lancet 2013 Jul 6;382

Forteo (PTH) (Cinopar)

Forteo (PTH) Increase bone formation at existing remodeling sites

Teriparatide Increase bone formation at existing remodeling sites Greater cost compared to other treatments Limited in severe osteoporosis or in patient who had progression despite of treatments No good effect on hip osteoporosis Duration of treatment in most studies 18 months but can use for 2 year

Teriparatide Use 20 mcg/d by sc injection Contraindicated in : Hypercalcemia Hyperparathyroidism Unexplained elevated ALP Exposure to external beam radiation or prior skeletal radiation

Strontium Ranelate : Trace element with Dual action Predominantly taken up by adsorption onto bone mineral Agonist of calcium -sensing receptor(independent PTH ,1 25 D) Dose 1-2gr/d After 3y has 11.5% increase in lumbar BMD & 41% in Fx rate References: 1. Spector TD. Rheum Dis Clin North Am 16:513-537, 1990. 2. Alarcón GS. Rheum Dis Clin North Am 21:589-604, 1995. 3. Goronzy JJ, Weyand CM, in Klippel JH (ed), Primer on the Rheumatic Diseases. 11th ed. Atlanta, Ga: Arthritis Foundation, 1997, pp 155-161.

A review of available safety data for strontium ranelate (Protelos) has raised concern about its cardiovascular safety beyond the already recognised risk of venous thromboembolism. An analysis of randomised controlled trial data has identified an increased risk of serious cardiac disorders, including myocardial infarction (relative risk compared with placebo was 1.6 [95% CI 1.07–2.38]). Meeting highlights from the Committee for Medicinal Products for Human Use (CHMP) 22-25 April 2013

OP prolia BP severe spinal OP BP forteo BP

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