OsteoporosisAhmed Shaman

Department of Clinical Pharmacyshaman@ksu.edu.sa

Background Reading & References

• Drugs for Postmenopausal Osteoporosis. Treatment Guidelines from The Medical Letter 2008:6(74);67-74.

• Sundeep Khosla, M.D., and L. Joseph Melton III, M.D., M.P.H. Osteopenia. N Engl J Med 2007;356:2293-300.

• Dipiro Chapter 93

Introduction

• Osteoporosis is a common and often silent disorder causing significant morbidity and mortality and reduced quality of life

• It is associated with increased risk and rate of bone fracture • Common sites of fracture include the spine, hip, and wrist• The fractures associated with osteoporosis have an enormous impact

on individual patients • Acute pain• Chronic pain• Loss of mobility• Height loss• Depression • Nursing home placement• Death

Physiology & pharmacology of bone formation

Physiology & pharmacology of bone formation

Bone Mineral Density

Measurement of Bone Mineral Density

• Bone mineral density can be measured at various sites throughout the skeletal system

• Central (hip and/or spine)• Peripheral (heel, forearm, or hand)

• Various methods• Dual-energy x-ray absorptiometry (DXA)

• central and peripheral sites• Quantitative ultrasound• Peripheral quantitative computed tomography• Radiographic absorptiometry• Single-energy x-ray absorptiometry

• Central DXA is recommended for diagnosis due to inconsistencies in T-scores measured between different sites and by different methods

Peripheral sites

Interpreting BMD Data

• T-scores and Z-scores are used• T-score is the number of standard deviations from the mean bone

mineral density in healthy young white women• The Z-score is a similar measure that is corrected for age and gender

of the patient

Skeletal Disorders T-scores

Normal ≥ -1

Osteopenia Between -2.5 and -1.0

Osteoporosis < -2.5

Clinical Presentation and Diagnosis of Osteoporosis

• General• Many patients with osteoporosis are asymptomatic unless they experience a

fragility fracture

• Symptoms• Symptoms of fragility fracture include pain at the site of the fracture or

immobility

• Signs• Height loss (greater than 2 cm)• Spinal kyphosis (“dowager’s hump”)• Fragility fracture especially of the hip or spine

• Laboratory Tests• Lab tests are only useful to rule out secondary causes of osteoporosis

• Diagnostic Tests• Bone densitometry using DXA reveals a T-score at least -2.5 SD below the

mean

Laboratory Evaluation

• Identifying or excluding secondary causes• Hyperparathyroidism • Low 25-hydroxyvitamin D levels• Hyperthyroidism• Cancer

TREATMENT

• Pharmacologic and nonpharmacologic therapies are aimed at:

1. Preventing fractures and their complications2. Maintaining or increasing bone mineral density3. Preventing secondary causes of bone loss4. Reducing morbidity and mortality associated with

osteoporosis

Treatment

• Lifestyle modification• Calcium• Vitamin D• Bisphosphonates

• Alendronate• Risedronate• Ibandronate• Zoledronic Acid

Treatment (2)

• Hormonal Therapy• Raloxifene• Estrogen• Calcitonin• Parathyroid Hormone• Testosterone in some men

Lifestyle Modification

Drugs Causing Fall

•Medications associated with increased risk of falling• Drugs affecting mental status

• antipsychotics, benzodiazepines, tricyclic antidepressants, sedative/hypnotics, anticholinergics, and corticosteroids

• Drugs causing orthostatic hypotension• Some cardiovascular and antihypertensive

Calcium & Vitamin D

• Elderly patients or patients receiving proton pump inhibitors or H2-receptor antagonists may have added difficulty absorbing calcium supplements due to reduced stomach acidity→ Ca citrate or Ca acetate more soluble

Over 65 years Adults under 65 years

Calcium 1,500 mg / day 1,000 mg / day

Vitamin D 800 – 1,000 IU / day 400 – 800 IU / day

Calcium Adverse Events

• Constipation, bloating, cramps, and flatulence• Changing to a different salt form may alleviate

symptoms for some patients • Calcium salts may reduce the absorption of

• Iron• Some antibiotics, such as tetracycline and

fluoroquinolones (up to 50%)• Thyroid hormone• → separate time of administration

Bisphosphonates

• Bisphosphonates are first-line therapy for osteoporosis due to established efficacy in preventing hip and vertebral fractures

• Decrease bone resorption by binding active sites & inhibiting osteoclasts

• IV & PO formulations

Bisphosphonates

Bisphosphonates – Adverse Effects

• Oral: heartburn, esophageal irritation & esophagitis.• Must take with about 180–240 mL of water after

overnight fast & in upright position • Afterwards stay upright 30-60 minutes & don’t take

anything by mouth except water• IV: infusion reactions, atrial arrhythmias• Either (especially IV & with chronic use)

• Osteonecrosis of the jaw• Risk factors include

• Chemotherapy, radiotherapy, corticosteroids, infection or pre-existing dental disease

Bisphosphonates

• Bisphosphonates are not recommended for use in patients with esophageal abnormalities, hypocalcaemia, renal insufficiency or failure (creatinine clearance less than 30–35 mL/min)

• Bisphosphonates should not be taken with other medications or dietary supplements(↓absorption)

Bisphosphonates

Hormones

•Raloxifene: • Selective estrogen receptor modulator (SERM)

• Estrogen-like effects on bone (reduce bone resorption and decrease overall bone turnover)

• Prevents & treats osteoporosis, ↓ vertebral fractures by 30%• AE: Hot flashes, leg cramps & edema• Increase risk of thrombosis• Increase risk of fatal stroke

Hormones

•Estrogen (HRT)• Replacement in postmenopausal women• Prevents hip and veterbral fractures by 33%• Give with progestin if intact uterus to prevent

endometrial cancer• No longer recommended due to adverse effects

• Increase risk of cardiac death, MI, stroke, pulmonary embolism & breast cancer

• WHI and HERS studies

Other Pharmacotherapy

• Calcitonin• Inhibits osteoclasts• IM, SC (neutralizing antibodies) and intranasal• Treatment; causes nasal irritation• AEs including flushing, urinary frequency, nausea, vomiting, abdominal

cramping, and irritation at the injection site

• Teriparatide• Parathyroid Hormone, stimulates bone formation• Risk of hypercalcemia, orthostatisc hypotention • Treatment; black box warning for osteosarcoma

Treatment Overview

• For everyone• Calcium, Vitamin D

• Osteopenia (T score – 1.0 to 2.49)• Add Lifestyle Modification• Consider pharmacotherapy risk vs benefit

• Osteoperosis (T score - 2.5 or more)or fracture

• Add pharmacotherapy (likely bisphosphonate)