Osteoporosis

Clinical Pharmacy Lecture 5. By Dr. Ramy Mohamed.

Definition of Osteoporosis Etiology Symptoms Diagnosis Treatment.

What is Osteoporosis?. Osteoporosis is defined as a “skeletal disorder characterized by compromised bone strength or low bone mass predisposing a person to an increased risk of fracture . “ Brittle bone ” disease Osteoporosis is silent disease because there are no symptoms (what you feel ). Bone strength reflects the integration of bone mass Clinically , osteoporosis is categorized as postmenopausal, age-related, or secondary causes.

In this condition, a fracture can occur even after a minor injury, such as a fall. Any kind of fracture may occur, but the most common are fractures of the spine, hip, and wrist. Osteoporosis is not an inevitable part of aging, but is a disease that can be prevented and treated, provided it is detected early..

Epidemiology. Men experience fewer osteoporosis-related fractures (only approximately 20%) than women. Men's bones also have a mechanical advantage because the larger bone diameter makes them more fracture-resistant. The etiology of male osteoporosis tends to be multifactoria l. But in female is due to estrogen deficiency ..

Bone composition. The skeleton is composed of mostly cortical bone “compact” (80%) with some trabecular bone (20%). Trabecular bone “spongy” type is 10 times more metabolically active compared with cortical bone. Bone is made of collagen and mineral components. The collagen component gives bone its flexibility and energy-absorbing capability . The mineral component gives bone its stiffness and strength ..

Bone cells. There is two types of bone cell. Osteoblasts – help create new bone formation tissue Osteoclasts – help resorption of old bone tissue. The receptor activator of nuclear factor kappa B ligand (RANKL) stimulates mature osteoclast activation and bone adherence to resorb bone Imbalance between bone formation and bone resorption lead to osteoporosis..

Bone cells. Osteoclasts have the function to disrupt the Old bone tissue OSTEOCLAST A hyperactivity of osteoclasts is a of the causes of the onset osteoporosis A proper balance between osteoclasts and osteoblasts is the basis for a normal bone density OSTEOBLAST Osteoblasts have the function to produce the new bone tissue.

How the Skeleton Changes. Menopause. Peak Bone M ass.

Etiology of osteoporosis. 10. Genetics Diet Lifestyle Hormonal status Diseases Medications Bone loss Aging Skeletal factors - impaired bone quality Non -skeletal factors (t fall risk) Sutx)ptirnal peak bone rnass Skeletal factors - decreased density Reduced bone strengh (osteoporosis) Low trauma fractures.

Pathophysiology. 11. Bone loss occurs when bone resorption > bone formation , leading to high bone turnover and decrease bone mineral density (BMD ). Failure to reach a normal peak bone mass In addition, the increased quantity of immature bone that is not adequately mineralized leading reduced bone quality and structural integrity are impaired..

Common risk factors for osteoporosis. Female Postmenopausal Family history of osteoporosis Lack of exercise Small body frame Low calcium intake Vitamin D deficiency.

13. POSTMENOPAUSAL. Postmenopausal osteoporosis affects primarily trabecular bone (vertebral bone) with fractures occurring predominantly at vertebral and distal forearm sites. The rate of bone loss commonly accelerates at menopause due to a decline in estrogen hormone production. Estrogen deficiency increases bone resorption more than formation. Estrogen deficiency during menopause increases proliferation, differentiation, and activation of new osteoclasts and prolongs survival of mature osteoclasts.

14. Age-related osteoporosis. that affects both cortical and trabecular bone and leads to vertebral, hip, and wrist fractures . Age birth – 30 years osteoblasts > osteoclasts Age > 30 years osteoblasts = osteoclasts, then osteoblasts < osteoclasts after 50 years Bone resorption increases with age. Age-related osteoporosis occurs mainly because of calcium , and vitamin D deficiencies due to change in their absorption and metabolism leading to accelerated bone turnover and reduced osteoblast formation..

15. DRUG-INDUCED OSTEOPOROSIS. Secondary osteoporosis is caused by either diseases or medications on both bone types . Disease include hyperparathyroidism, rheumatoid arthritis, hypogonadism Systemic glucocorticoids, thyroid hormone replacement, some antiepileptic drugs, depot medroxyprogesterone acetate and heparin use. Some anticonvulsants, like phenobarbital and phenytoin , hasten vitamin D metabolism and the resultant effects can lead to osteoprosis . Heparin stimulate osteoclast activity , Low-molecular-weight heparins such as enoxaparin may pose less risk of bone loss..

Symptoms Usually, there are no symptoms of osteoporosis. That is why it is sometimes called a silent disease. However, you should watch out for the following things: Loss of height (getting shorter by an inch or more). Change in posture (stooping or bending forward). Shortness of breath (smaller lung capacity due to compressed disks). Bone fractures. Pain in the lower back..

Diagnosis. Osteoporosis is diagnosed by BMD (bone mineral density) measurement or presence of a fragility fracture . Many patients are unaware they have osteoporosis until testing for a fracture . For secondary causes : Thyroid-stimulating hormone, parathyroid hormone, complete blood count, creatinine , liver enzymes, calcium, phosphorus, alkaline phosphatase, 25-hydroxyvitamin D..

18. Bone density measurement. . Measurement of central (hip and spine) BMD with dual-energy x-ray absorptiometry (DXA) is the gold standard for osteoporosis diagnosis predict fracture risk, and influence treatment decisions. A T-score is a comparison of the patient’s BMD to BMD of a healthy population. The T-score is the number of standard deviations from the mean of the reference population. Osteoporosis is a T-score at or below –2.5 ..

DXA.

DXA. Simple test that measures bone mineral density. Often the measurements are at your spine and your hip, including a part of the hip called the femoral neck, at the top of the thigh bone (femur). The test is quick and painless..

-4 -3 -2.5 +1 +2 Normal +3 Osteoporosis. DXA. World Health Organization Diagnostic Criteria.

DXA test results are scored compared with the BMD of young, healthy people..

The categories for BMD. Estrogen deficient women undecided about taking hormones. Those with spinal abnormalities or X-ray evidence of bone loss. Anyone taking long-term corticosteroid treatment (such as Prednisone). Primary hyperparathyroidism with no symptoms. Monitoring of therapy for osteoporosis..

24. Treatment Outcomes. Reducing pain and deformity, and improving quality of life Optimize and stabilize bone mass Reduce the future incidence of osteoporosis Improving functional capacity and mobility Identify risk factors for developing osteoporosis and resolve reversible risks. This require both pharmacologic and non-pharmacologic treatment.

NON- PHARMACOLOGICAL TREATMENT.

26. NON PHARMACOLOGICAL TREATMENT. Because excessive caffeine consumption increases calcium excretion , caffeine intake should ideally be limited. Smoking cessation : Cigarette smoking is associated with up to an 80% increased relative risk for hip fracture. Alcohol increased risk for osteoporosis. Alcohol increases bone resorption by increasing RANKL and decreases bone formation by increasing oxidative stress Physical activity or exercise prevents osteoporotic fractures. It decrease the risk of falls and fractures by improving muscle strength, coordination, balance, and mobility ..

27. Diet. A well-balanced diet with adequate calcium and vitamin D is essential for healthy bones mainly Dairy products (milk and cheese). Isoflavones : phytoestrogens are plant-derived compounds that possess weak estrogenic agonist and antagonist effects throughout the body EX: Genistein is isoflavone in soybeans available as a supplement or part of a calcium combination product..

PHARMACOLOGICAL THERAPY.

Calcium. Taken in adequate amounts to prevent bone destruction. Usually combined with vitamin D and osteoporosis medications Calcium carbonate ( Calcimate ®) is the salt of choice because it contains the highest concentration of elemental calcium (40%) . It should be ingested with meals to enhance absorption from increased acid secretion . Calcium citrate : absorption is acid independent and need not be taken with meals. No more than 1200–1500 mg/day SE: Constipation treated with increased water intake, and dietary fiber.

Vitamin D. Recommended for all patients with osteoporosis; promotes calcium reabsorption . Minimum dose is 800 international units/day for those older than 70 years, 600 international units/ day 70 years of age and younger and 800– 1000 international units/day for those 50 and older. Higher doses of vitamin D may be necessary for those with vitamin D concentrations less than 30 ng / mL . Usually found as alone or combination with calcium or as alfacalcidol “Bone one®”(vitamin D precursor).

Bisphosphonates. This class of drugs (often called “ antiresorptive ” drugs ) ( eg . Alendronate (Fosamax), risedronate (Actonel), ibandronate ( bonaprove ), zoledronic acid) -Binds to bone, inhibits osteoclast activity bisphosphonates provide the greatest BMD increases and fracture risk reductions. BMD increases are dose dependent . After discontinuation, the increased BMD is sustained for a prolonged period for years Taken once daily, once weekly, once monthly ..

Bisphosphonates. -Available in tablet mainly or may injectable forms (IV) - Take on empty stomach in the morning with at least 200 ml of plain tap water (not coffee, juice, mineral water, or milk) Remain upright and do not eat for ½-1 hour after taking Duration of bisphosphonate therapy has not been defined , but safety data exist for periods of 10 to 13 years adverse effects are Esophageal, gastric, or duodenal irritation, perforation, ulceration, or bleeding . Also, nausea, abdominal pain, and dyspepsia..

Bisphosphonate Medications for Osteoporosis (OP) Generic drug name Approved uses for OP Dosing and form Alendronate Prevention and treatment of postmenopausal OP in women Treatment of OP due to use of glucocorticoid medicines 10 mg/day or 70 mg/week. Alendronate with vitamin D: 70 mg/week with 2800 international units of vitamin D3 Tablet Risedronate Prevention and treatment of postmenopausal OP in women Prevention and treatment of OP due to use of glucocorticoid medicines 5 mg/day or 35 mg/week or 150 mg once monthly Tablet Ibandronate Prevention and treatment of postmenopausal OP in women 150 mg once monthly orally or every three months by intravenous infusion (often called IV) given through a vein Zoledronic acid Same as for risedronate 5 mg once a year by IV.

Bisphosphonates. ONCE WEEKLY FOSAMAX' 70 mg •bendtonate sodium tablets.

Denosumab ( Prolia ). Denosumab is FDA approved for treatment of osteoporosis in women and men at high risk for fracture. Also, to prevent osteoprosis for men receiving androgen-deprivation therapy for nonmetastatic prostate cancer and in women receiving adjuvant aromatase inhibitor therapy for breast cancer. Denosumab is a fully Inhibits osteoclast-mediated bone resorption ; monoclonal antibody against receptor activator of nuclear factor қ β ligand (RANKL) (cytokine essential for formation, function, survival of osteoclasts ) 60 mg subcutaneously every 6 months No dosage adjustment is necessary in renal impairment.

Denosumab. The BMD effects are similar to weekly alendronate. The product is available as a refrigerated prefilled pen or single-use vial administered subcutaneously Denosumab was generally well tolerated. Dermatologic reactions not specific to the injection site such as dermatitis, eczema, and rash. Serious infections including skin infections. If any signs of skin infection such as cellulitis..

Selective estrogen receptor modulators 1- Raloxifene ( Evista ).

Human parathyroid hormone related peptide analogs.

2- Abaloparatide ( Tymlos ) Regulates bone metabolism, intestinal calcium absorption, and renal tubular calcium and phosphate reabsorption. Indication : Treatment of postmenopausal women with osteoporosis that have a high risk of fracture . Precautions (1) Orthostatic hypotension: patient should be instructed to sit or lay down ( 2) Hyperkalemia: avoid in patients at risk for hypercalcemia (3) Hypercalciuria and urolithiasis : monitor urine calcium Dose : 80 mcg/day subcutaneously; patients should also take supplemental calcium and vitamin D.

Hormone released from the thyroid gland Binds to osteoclasts, inhibits bone resorption Salmon -derived because more potent and longer lasting Less effective than other treatments (third line) Helpful in reducing pain from fractures of spine mainly. it should be prescribed for short-term treatment (4 weeks) Nasal spray is most popular preparation > SC route. The intranasal dose is 200 units daily, alternating nares every other day. Subcutaneous administration of 100 units daily is available but rarely used because of adverse effects ( allergic reaction, rhinitis and epistaxis ) and high cost.

EVALUATION OF THERAPEUTIC OUTCOMES. BMD measurements can be obtained every 1 to 2 years for monitoring bone loss and treatment response. Patients should be asked about possible fracture symptoms (e.g., bone pain, disability) at each visit . Medication adherence and tolerance and side effects should be evaluated at each visit..

Points to remember. Make sure there is enough calcium and vitamin D in your diet. Be physically active and do weight-bearing exercises, like walking, most days each week. Change lifestyle choices that raise your risk of osteoporosis..

Eat high-calcium foods, exercise regularly and do not smoke at young age to prevent ....

Don 't let Your bones age faster than You- STOP OSTEOPOROSIS NOW For healthy bone consult your doctor.

aůThank ) You. 45.