Salman Bin AbdulAziz University College Of Pharmacy Osteoporosis Pathophysiology PHCL 415

Case 1 K..M is a 72-year-old retired train driver who was admitted to hospital six months ago after fracturing his hip, when his foot got caught on a floor mat at home. K.M has been reluctant to walk every evening since this fall. He has been a smoker for 30 years and smokes 15 cigarettes every day. He lives alone in the self-catered accommodation part of a retirement village and has lost about 5 kg of weight in the past few months. His diet has deteriorated since his wife passed away two years ago. His daughter accompanies him to visit his GP, as she is concerned about his recent weight loss.

His current medicine history includes ramipril 5 mg once daily in the morning for well controlled hypertension, he ‘s taking omeprazole for a a year and occasionally temazepam 10 mg at bedtime to help him sleep. On examination blood pressure is 115/78 mmHg and he has no significant family medical history. His vitamin D level is moderately deficient (22 nmol/L) and a bone mineral density test T-score in the hip is –1.8 and in the spine is –2.7, confirming a diagnosis of osteoporosis.

Define osteoporosis ? Bone disorder characterized by low bone mineral density (BMD), impaired bone architecture, and compromised bone strength predisposing to increased fracture risk. Osteoporosis effects women more than men ? True/ False

True or false ? Osteoporosis effects women more than men ? True/ False Postmenopausal White women have 50% lifetime chance of developing osteoporosis-related fracture, whereas men have 20% lifetime chance.

Pathophysiology Men and women begin to lose bone mass starting in third or fourth decade because of reduced bone formation. Mechanism of post-menopause osteoporosis in women ? Etiology of osteoporosis in males ? Estrogen deficiency during menopause increases osteoclast activity, increasing bone resorption more than formation. secondary causes and aging

Pathophysiology How aging can cause osteoporosis ? Age-related osteoporosis occurs because of hormone, calcium, and vitamin D deficiencies leading to accelerated bone turnover and reduced osteoblast formation.

Pathophysiology Drug induced osteoporosis ? One of the following medication can be a cause of mr K.M condition ? Omeprazole Ramipril Temazepam

Pathophysiology Drug induced osteoporosis ? One of the following medication can be a cause of mr K.M condition ? Omeprazole (PPI) Ramipril (ACE Inhibitors) Temazepam (Benzodiazepines-Hypnotics)

Pathophysiology Drug induced osteoporosis ?

Pathophysiology Chronic kidney disease can cause osteoporosis ? (T/F) Mention some conditions that cause secondary osteoporosis ? True

MCQ ! K.M risk factors include the following except ? Smoking Male gender Advance age PPI use

MCQ ! K.M risk factors include the following except ? Smoking Male gender Advance age PPI use

RISK FACTORS Low BMD Female sex Advanced age Race/ethnicity History of previous low trauma (fragility) fracture Osteoporotic fracture in first-degree relative Low body weight or body mass index Premature menopause (before age 45) Secondary osteoporosis (especially rheumatoid arthritis) Past or present systemic oral glucocorticoid therapy Current cigarette smoking Alcohol intake of 3 or more drinks per day Low calcium intake Low physical activity Minimal sun exposure

PREVENTION AND SCREENING ……………………….. (test) can be used for the measurement of BMD Measurement of BMD at peripheral sites (forearm, heel, and phalanges) with ultrasound or dual-energy x-ray absorptiometry (DXA) scan used for screening and to determine need for further testing.

Diagnosis Means of Confirmation and Diagnosis Presence of low-trauma fracture, or Central hip or spine DXA scan using World Health Organization (WHO) T-score thresholds T-scores from DXA measurement of central (hip and spine): Normal bone mass: Greater than –1 Osteopenia: –1 to –2.4 Osteoporosis: At least –2.5

Clinical Presentation /Signs and Symptoms Fragility fracture may be first sign of osteoporosis; fractures can occur after bending, lifting, falling, or independent of any activity. Most common fracture sites are vertebrae, proximal femur, and distal radius (wrist or Colles fracture). Two thirds of patients with vertebral fractures asymptomatic; the remainder present with back pain that radiates down leg after new vertebral fracture.

Clinical Presentation /Signs and Symptoms Pain usually subsides after 2–4 weeks, but chronic residual low back pain may persist. Patients with nonvertebral fractures frequently present with pain, swelling, and reduced function and mobility at fracture site. Physical examination findings include postural changes (kyphosis) and loss of height (more than 1.5 in [3.8 cm]).

Fill in the blanks Question Postural changes in kyphosis means? Most common fracture site…………? Two thirds of patients with vertebral fractures are………..? Fragility fracture may be first sign of osteoporosis; fractures can occur after ………………………………….?

•Two thirds of patients with vertebral fractures are asymptomatic? Fill in the blanks Question •Postural changes- kyphosis means abnormal curvature of thoracic spine? •Most common fracture site are vertebrae, proximal femur, and distal radius? •Two thirds of patients with vertebral fractures are asymptomatic? •Fragility fracture may be first sign of osteoporosis; fractures can occur after bending, lifting, falling, or independent of any activity?

Case Presentation Mr. JM , 64-year-old retired firefighter Case Study 2 Case Presentation Mr. JM , 64-year-old retired firefighter Retired nine years ago; now doing contract carpentry Presents for physical examination, complaining his back has been “worse than usual” the past three weeks On no medications Two drinks per week. Prior smoker (45 pack/year history) Quit smoking one year ago

Physical Examination Height: 180 cm (5'11") Patient recalls being 185.5 cm (6'1") Weight: 80 kg (up 5 kg from one year ago) Body mass index (BMI): 24.7 kg/m2 Changes in height and weight can be signs of vertebral fractures Other indicators of vertebral fracture in physical examination: Rib-pelvis distance and occiput-wall distance

Risk Factor Assessment Family history: none significant No history of systemic glucocorticoids or androgen-deprivation therapy No history of secondary causes of osteoporosis Historical height loss No previous trauma Alcohol use: approximately two drinks per week

Q. What tests would you consider ordering? Screening for osteoporosis with dual energy X-ray absorptiometry (DXA). T-score -1.9 at femoral neck Lateral thoraco-lumbar spine X-ray is ordered to rule out vertebral compression deformities The radiologist makes note of two vertebrae being wedge shaped and just meeting the criteria for vertebral compression fracture.

Considerations for Therapy The guidelines do recommend that diagnosis and treatment decisions should be based on a validated 10-year risk-assessment tool (i.e., CAROC or FRAX) FRAX predicts 12% risk (moderate)1 However, the presence of multiple vertebral fractures in this case place Mr. JM at high risk In fact, 10-year assessment tools underestimate risk in patients with vertebral fractures

Treatment Considerations Bloodwork to rule out secondary causes of osteoporosis Assume vitamin D level is low and start supplementation (with calcium) Pharmacotherapy is indicated for a high-risk patient

Conclusions Mr. JM is high risk because of his vertebral fractures In this case, 10-year assessment tools underestimate risk Patients at high risk benefit from pharmacologic therapy Recommended agents for first-line use in men are alendronate, risedronate, or zoledronic acid

Few Facts: FOSAMAX (alendronate sodium) is a bisphosphonate that acts as a specific inhibitor of osteoclastmediated bone resorption.

PTH (Parathyroid Hormone) Secreted by the parathyroid gland. It increases the calcium levels in the blood, which decreases calcium levels in the bone. Calcitonin Secreted by the thyroid gland. It decreases the calcium levels in the blood, which increases the calcium levels in the bone. calcium and bone health Calcium is vital to the strength of bones. 99% of body's calcium is stored in the bone. Calcium deficiency can affect bone strength.

importance of Vitamin D to calcium Increases up to 30-80% of calcium absorption. Exposure to UV light (sun light) for about 15 minutes to get Vitamin D. calcium supplements Most common supplement: Calcium Carbonate - daily dose: 1,000-1,500 mg/day effects of alcohol, caffeine, and sodium on calcium Increases urine output and calcium loss occurs through urine. HRT Hormone Replacement Therapy. Made of estrogen and progesterone. Intended for menopausal women.