osteoporosisIntan Rahmania Eka D

Osteoporosis

The term osteoporosis is derived from the Greek words osteon (bone) and poros (pore). Although osteoporosis has many definitions, the World Health Organization (WHO) defines it as a disease “characterized by low bone mass and microarchitectural deterioration of bone tissue, leading to enhanced bone fragility and a consequent increase in fracture risk”

Epidemiologi• Currently affecting more than 10 million people in the United

States. • osteoporosis is projected to impact approximately 14 million

adults over the age of 50 by the year 2020.• Worldwide, approximately 200 million women have

osteoporosis.

Osteoporosis

PRIMERbila sebabnya tidak

diketahui

SEKUNDER bila sebabnya

diketahui Tipe IPada wanita umur antara 51–75 tahun, & berhubungan dengan berkurangnya estrogen pada masa transisi menopause.

Tipe IPada wanita umur antara 51–75 tahun, & berhubungan dengan berkurangnya estrogen pada masa transisi menopause.

Tipe II (Senile Osteoporosis)Sering terjadi pd umur > 60 thn. Pd ♀ & ♂ mempunyaipatofisiologi yang berbeda, meskipun estrogen mungkin memegang peranan pd tipe II osteoporosis.

Tipe II (Senile Osteoporosis)Sering terjadi pd umur > 60 thn. Pd ♀ & ♂ mempunyaipatofisiologi yang berbeda, meskipun estrogen mungkin memegang peranan pd tipe II osteoporosis.

Osteoporosis yang

didasari suatu

penyakit atau

pengobatan, yang

merusak tulang.

Osteoporosis yang

didasari suatu

penyakit atau

pengobatan, yang

merusak tulang.

Bone remodeling

Estrogen• supresing production and defferentiation of osteoclast• increasing osteoclast apoptosis• decrease production of several cytokin (IL 1, IL 6, TNF)• decrease production of RANKL (inhibit mature of osteoclast)• decrease of osteoprotegerin (OPG)

Vit D, Parathyroid Hormon, and calcium• vit D and parathyroid hormon work to maintain calcium

homeostasis.• UV B7-Dehidrocholesterol (skin) cholecalciferol (vit D3)• From dietary cholechalciferol (Vit D3 ) + ergocalciferol (vit

D2)• cholechalciferol (Vit D3 ) + ergocalciferol (vit D2)25

hydroxyvitaminD (25(OH)D) (liver)• PTH via 25(OH)vit D 1α hydroxylase• 25 hydroxyvitamin D 1,25-dihidroxyvit D

(calcitriol) (kidney)

• Calcitriol bind to intestinal reseptor and increase absorbtion of calcium n phosphorus

Calcium Homeostasis

Etiology

Risk Factor

Clinical Manifestation• many patients are unware and present only after fracture• pain, immobility, depression, fear, and low self esteem from

physical limitation and deformities• sign : shortened statur, kyphosis, or lordosis fracture

low bone density or radiography• Laboratory : CBC, Cr , Ca, Posphate, ALP, Albumin, TSH, 25 (OH) vit

D, 24-H urine concentration of Ca n Phospate• Pemeriksaan :

• DXA (dual energy x ray absorbtiometryVertebra Fracture Assesment with DXA

technology• Radiograph

Treatment• Non pharmacology Therapy :

Diet : Alcohol, caffein dan carbonate cola beverage calcium supplement

• Vit D • Vit K osteocalcin bone formation• Isoflavon phytoestrogen• Exercise : jogging, golf, walking 30 min/day at least 2/weeks• Fall prevention

Pharmacology• combination calcium, vit D suplement and biphosphonate is

drug of choice.E-BOOK\__Pharmacotherapy__8th_Edition__2011_.chm

Biphosphonate (Alendronate, Risedronate, and ibandronate)• bone resorption inhibitor• blocking and inhibiting triphosphatase-signaling protein

↓ osteoclast maturation, number, bone adhesion, and life span.

• Alendronate : 5 mg/day, or 35 mg/weekly (prevention), 10 mg/day or 70 mg with vit D 2800, 5600 U.

• Patients should not lie down, but should stay fully upright for at least 30 minutes (60 minutes for ibandronate) after ingesting an oral bisphosphonate to prevent esophageal irritation or ulceration and to ensure appropriate bioavailability

• Patients should ingest adequate calcium and vitamin D, but should not take the calcium or vitamin D at the same time as the alendronate

• jika pasien lupa 1 hari tidak minum obat boleh dilanjutkan dosis selanjutnya, jika lupanya lama maka tunggu 7 hari sebelum pemakaian berikutnya.

Mixed Estrogen agonis/antagonist/Selective Estrogen Receptor Modulators

• Raloxifene has estrogen agonist in bone and antagonist action in breast and uterine tissue

• decrease vertebral fracture and increase spine and hip BMD.• Hot flushed greater likehood women finishing menopouse or

discontinue estrogen therapy• benefit for women who has osteoporosis and breast cancer

risk• decrease LDL, neutral for HDL, increase TG• contraindicated for patient who has VTE• Cholestyramine, when coadministered with raloxifene, may

decrease raloxifene absorption by 60% because of its effects on enterohepatic cycling

Calcitonin• third line terapies• less benefit than antiresorptive therapies• is an endogenous hormon released from thyroid gland when

calcium is elevated• Calcitonin has been studied for the prevention of

glucocorticoid-induced osteoporosis as well

Denosumab• dosis : 60 mcq subcutaneously every 6 months• fully monoclonal antibody bind RANKL inhibitor

osteoclastogenesis and promote osteoclast apoptosis• Adverse effect : back, extrimity, and musculoskeletal

pain, ,hipercholesterolemia.

Testosteron• Decrease testosteron concentrations are seen with certain

gonadall disease, eating disorder, glucocorticoid therapy, oophorectomi and also menopouse andandropouse.

Anabolic Therapies• increase bone formation• Recombinan product representing at the first 34 amino acid in

PTH• Teriparatide• Transient hipercalcemia• Strontium ranelate has antiresorptive and mild anabolic

effects. The exact mechanism of action remains unknown• Nausea and vomiting have been associated with oral dissolved

strontium, which abated after 3 months of therapy.

Medications Comments

AIDS/HIV medications

Nucleoside reverse transcriptase inhibitors (antiretroviral therapy, ART) (zidovudine, didanosine, lamivudine)

BMD (ART > PI), no fracture data; increased osteoclast activity and decreased osteoblast activity

Protease inhibitors (PI) (nelfinavir, indinivir, saquinavir, ritonavir, lopinavir)

Anticonvulsant therapy (phenytoin, carbamazepine, phenobarbital, valproic acid)

BMD and fracture risk; increased vitamin D metabolism leading to low 25(OH) vitamin D concentrations

Aromatase inhibitors (e.g., letrozole, anastrozole) BMD and fracture risk; reduced estrogen concentrations

Furosemide fracture risk; increased calcium renal elimination

Glucocorticoids (long-term oral therapy) BMD and fracture risk; dose and duration dependent; see special populations section

Gonadotropin-releasing hormone (GnRH) agonists or analogs (e.g., leuprolide, goserelin)

BMD and fracture risk; decreased sex hormone production

Heparin (unfractionated, UFH) or low molecular weight heparin (LMWH)

BMD and fracture risk (UFH >>> LMWH) with long-term use (e.g., >6 mo); decreased osteoblast function and increased osteoclast function

Medroxyprogesterone acetate depot administration (DMPA) BMD, no fracture data; possible BMD recovery with discontinuation; central DXA monitoring of BMD recommended with 2 years of use; decreased estrogen concentrations

Proton pump inhibitor therapy (long-term therapy) vertebral and hip fracture risk; possible calcium malabsorption secondary to acid suppression for carbonate salts

Selective serotonin reuptake inhibitors hip fracture risk; decreased osteoblast activity

Thiazolidinediones (TZDs) (pioglitazone, rosiglitazone) BMD and fracture risk; risk may be greater in women than men; decreased osteoblast function

Thyroid—excessive supplementation BMD and fracture risk (> in men); risk increases with TSH concentration <0.1 IU/mL (<0.1 mIU/L); possible increase in bone resorption

Vitamin A—excessive intake (1.5 mg of retinol form) BMD and fracture risk; decreased osteoblast activity and increased osteoclast activity