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OSTEOPORO SIS

It is a condition characterized by the loss of the normal density of bone, resulting in fragile bone. Osteoporosis leads to literally abnormally porous bone that is more compressible like a sponge, than dense like a brick.

This disorder of the skeleton weakens the bone causing an increase in the risk for breaking bones (bone fracture). Osteoporosis is called the silent disease because

1. Postmenopausal osteoporosis affects primarily cancellous bone in the decade after menopause 1. Age-related osteoporosis results from bone less that begins shortly after peak bone mass is obtained and affects both compact and cancellous bone

3. Secondary osteoporosis
caused by certain medications and diseases and affects both types of bone.

There are three major types of bone "cells" a. Osteoblasts b. Osteoclasts c. Osteocytes Osteoblasts deposit bone. Osteoblasts also secrete large amounts of alkaline phosphatase when they are active and this is thus used as a measure of bone activity. Some osteoblasts become encased within the bone matrix and the "Osteocytes" or the bone cells. Osteoclasts absorb bone and are under the influence of parathyroid hormone and a number of local factors that may be secreted by the osteoblasts. Bone is constantly being remodeled. Remodeling is extremely important in that it allows the bone to renew itself, grow to deal with specific stressors, and repair microfractures or other trauma.

OSTEOPOROSIS is essentially caused by aberrations in bone remodeling and more of bone resorption than formation, leading to bone fragility.

It is the number of standard deviations from the mean bone mineral density (BMD) for the young normal population. Bases of the WHO classifying bone mass. in

Osteopenia is a condition where Bone Mineral Density is lower than normal. It is considered to be a precursor to Osteoporosis.

Personal Characteristics o Advanced age o Female o White (fair, thin skin) o Small bone structure o Postmenopausal o Family History o Personal history of fracture as an adult;

Lifestyle o Sedentary o Long term calcium deficiency o High-protein diet o Excessive alcohol intake o Excessive caffeine intake o smoking oPoor nutrition and poor general health

Drug and disease related


o Aluminum-containing antacids o Anticonvulsants o Heparin o Corticosteriods or Cushings disease o Gastrectomy

o Diabetes mellitus o Chronic Obstructive o Lung Disease o Malignancy o Hyperthyroidism o Hyperparathyroidism o Rheumatoid Arthritis

Pain accompanied by skeletal fractures A vertebral compression fracture or fractures of the hip pelvis humerus or any other bone. Dowager's hump A curved upper back also known as Lordosis

Compression fractures in the spine may cause severe back pain. Shortened stature Kyphosis forward rounding of your upper back Also known as Hunchback

NON-PHARMACOLOGIC Balanced diet Adequate intake of calcium and vitamin D. Calcium supplements if necessary. Avoidance or elimination of coffee intake. Elimination of Smoking Weight-bearing aerobic and strengthening exercises

PHARMACOLOGIC Antiresorptive Therapy Calcium Vitamin D and Metabolites Bisphosphonates Selective Estrogen Receptor Modulators (SERMs) Calcitonin Estrogen and Hormonal Therapy Phytoestrogens Testosterone and Anabolic Steroids

Bone Formation Therapy


Teriparatide (Parathyroid Hormone)

Calcium
o should be ingested in adequate amounts to prevent secondary hyperparathyroidism and bone destruction. o Higher calcium intake prevents or reduces bone loss in adults. o effects are enhanced when combined with other anti-resorptive therapies or exercise. o combination with vitamin D decreases fractures.

Calcium

Available forms:
Calcium carbonate (40%) Calcium carbonate with vitamin D Calcium citrate (24%) Calcium phosphate tribasic (39%)

Calcium carbonate salt of choice it contains the highest concentration of elemental calcium (40%) the least expensive ingested with meals to enhance absorption from increased acid secretion.

Calcium
Calcium citrate absorption is acid independent need not be taken with meals. Adverse Effect: Constipation is the most common reaction Treatment: increased water intake, dietary fiber (given separately from calcium), and exercise. o Calcium carbonate can create gas, sometimes causing flatulence or upset stomach.

Vitamin D and Metabolites It increases BMD, and it may reduce fractures. adult intake should be 800 to 1000 units daily.

Bisphosphonates

MOA: bind to hydroxyapatite in bone and decrease resorption by inhibiting osteoclast adherence to bone surfaces. The estimated terminal half-lives of bisphosphonates reflect the slow rates of bone turnover (many years). It provides the greatest BMD increases and fracture risk reductions 5% to 8% increase (lumbar spine) 2% to 4% increase (femoral neck).

Bisphosphonates
Alendronate, risedronate, and ibandronate FDA approved for prevention and treatment of postmenopausal osteoporosis Alendronate is also approved for osteoporosis in men. Alendronate and risedronate are indicated for corticosteroid-induced osteoporosis.

Bisphosphonates
Adverse Effects: nausea, abdominal pain, and dyspepsia. Esophageal, gastric, or duodenal irritation, perforation, ulceration, or bleeding may occur when administration directions are not followed or when bisphosphonates are prescribed for patients with contraindications.

Selective Estrogen Receptor Modulators (SERMs)


Raloxifene an estrogen agonist in bone tissue but an antagonist in the breast and uterus. approved for prevention and treatment of postmenopausal osteoporosis. increases spine and hip BMD by 2% to 3% and decreases vertebral fractures.

Selective Estrogen Receptor Modulators (SERMs) Raloxifene well tolerated overall, but hot flushes occasionally cause women to discontinue therapy associated with a threefold increased risk of venous thromboembolism, similar to the risk with estrogen. contraindicated in women with active thromboembolic disease.

Calcitonin
o released from the thyroid gland when serum calcium is elevated. o Salmon calcitonin used clinically - more potent and longer lasting than the mammalian form. Pharmacologic doses decrease bone resorption. o indicated for osteoporosis treatment for women at least 5 years past menopause.

Calcitonin onot FDA approved for osteoporosis in men. oA 200-unit regimen of nasal calcitonin increased spine BMD and reduced new vertebral fractures by 36%. oCalcitonin does not consistently affect hip BMD and does not decrease hip fracture risk.

Estrogen and Hormonal Therapy


o Mechanism of action decrease osteoclast recruitment and activity inhibit PTH peripherally increase calcitriol concentrations and intestinal calcium absorption decrease renal calcium excretion. o Most gains in BMD were seen within the first few years of treatment

Estrogen and Hormonal Therapy


o Effects on BMD are increased when ET or HT is combined with bisphosphonates or parathyroid hormone. o HT was shown to decrease vertebral, hip, and all fractures by 34%, 34%, and 24%, respectively. o the beneficial bone benefits of ET and HT do not outweigh their negative effects.

Estrogen and Hormonal Therapy onot advocated for prevention of osteoporosis and fractures, because other better and safer medications exist. oThe lowest dose is used for preventing and controlling menopausal symptoms, with use discontinued upon symptom abatement.

Phytoestrogens
o most common forms: isoflavonoids (soy proteins) lignans (flaxseed) o Beneficial bone effects may be related to bone estrogen receptor agonist activity or effects on osteoblasts and osteoclasts. o They can be used for preventive bone-sparing effects but are probably not sufficient when used alone for treatment.

Testosterone and Anabolic Steroids


omethyltestosterone Gives an increase in BMD oAnabolic steroids (nandrolone decanoate) have shown minimal to no effect on BMD but do increase muscle strength.

Teriparatide (Parathyroid Hormone)


o contains the first 34 amino acids in human PTH. o therapeutic doses for shorter periods improve BMD and reduce fracture risk. o In postmenopausal women with osteoporosis and preexisting fractures, teriparatide reduced the risk of new vertebral fractures by 65% compared with placebo.

Teriparatide (Parathyroid Hormone) oIn men with osteoporosis, teriparatide increased BMD, but its impact on fracture rate remains undetermined. ocontraindicated in patients with Paget's disease of the bone, unexplained alkaline phosphatase elevations, or a history of previous skeletal radiation therapy.

Teriparatide (Parathyroid Hormone)


o Not used with alendronate may blunt teriparatide's beneficial effects.

o Because of adverse effects and cost concerns, teriparatide is reserved for patients at high risk of osteoporosis-related fracture who cannot or will not take or have failed bisphosphonate therapy.

TF, a 66-year-old female; outpatient clinic

New-onset back pain, joint and stomach pain

TF complains of back pain for 2 days duration and joint pain and stomach pain not relieved by antacids.

TF has rheumatoid arthritis for 10 years treated with prednisone after failed therapy with NSAIDS with a history of NSAID-induced peptic ulcer disease and chronic alchoholism, postmenopausal for four years and is status post a hip fracture after fall in a bathtub a year ago.

TFs husband died three years ago; since then, lives with daughter who is married with two

Tobacco (+) 22 pack/year history. Alcohol(+) 4-6 drinks per day in the past; denies use presently, but daughter reports she began drinking again

Prednisone 5mg PO QD Ranitidine 150mg PO QHS Aluminum hydroxide 200mg magnesium hydroxide 200mg suspension PO as needed.

NO KNOWN DRUG ALLERGIES

GEN: Thin, elderly appearing Caucasian woman in no acute distress VS: BP 140/85, HR 70, RR 14, Wt 55kg, Ht 160cm (ht at last visit 6 months ago:160 cm) HEENT: WNL COR: Normal S1 and S2 CHEST: Clear to auscultation and percussion

ABD: Soft, nontender; liver palpable; hepatomegaly GU: WNL RECT: Guaiac negative EXT: Muscle atrophy in dorsal musculature and joint swelling of both hands NEURO: Alert, 0 x 3 H. pylori ( - )

Problem 1: Osteoporosis Problem 2: Rheumatoid Arthritis Problem 3: Peptic Ulcer Disease Problem 4: Hypertension Problem 5: Liver Damage due to Chronic Alcoholism Problem 6: Anemia Problem 7: Smoking

1. Osteoporosis
Subjective: New-onset back pain, hip fracture after fall in a bathtub 1 year ago Assessment:

o The patient has developed Glucocorticoidinduced Osteoporosis, after 10 years treatment with prednisone manifested by new-onset back pain. A hip fracture after a fall in a bathtub one year ago contributed to the development of osteoporosis.

Plan
Non Pharmacologic Treatment stop smoking avoid alcohol intake eliminate hazards that can increase the risk of falling Pharmacologic Treatment Alendronate ( Fosamax ) 10 mg PO 1 tab OD Calcium carbonate 300mg + vit D3 150 IU PO 1 tab OD -Dose interval should be monitored

Renal insufficiency FOSAMAX is not recommended for patients with renal insufficiency (creatinine clearance < 35 mL/min)

ClCr = (140-age) X BW X Factor SrCr (mg/dL) x 72 ClCr = (140-66) X 55 X 0.85___

2. Rheumatoid Arthritis Subjective: joint pain Objective: joint swelling of both hands rheumatoid arthritis for 10 years Assessment: oThe patient is having Rheumatoid Arthritis characterized by joint pain and swelling of the joint in both hands.

Plan:
Non Pharmacologic Treatment o exercise regularly o physical and occupational therapy o rest o orthostatic support device Pharmacological Treatment oDiscontinue Prednisone oHydroxychloroquine sulfate 400 mg once daily. Take with Food. Monitor Ophthalmologic and CBC count.

3. Peptic Ulcer Disease


Subjective: stomach pain, history of NSAIDInduced Peptic Ulcer Objective: Ranitidine 150mg PO QHS Assessment: o The patient has a recurring peptic ulcer characterized by stomach pain. Ranitidine and Antacid treatment does not help in treating the disease.

Plan:

Stop Ranitidine and antacid treatment Take Sucralfate 1g 4 times a day.

4.

High Blood Pressure Objective: BP 140/85

Assessment: The patients blood pressure is above the normal values of 120/80.

Plan:
Non-Pharmacological Therapy

Low sodium diet Low fat diet Pharmacological Therapy Nifedipine 5mg capsule twice a day. Monitor HR, BP and signs and symptoms of CHF.

5. Liver Damage due to Chronic Alcoholism


Subjective: PMH of chronic alcoholism, (+) 46 drinks per day Objective: AST and ALT (35U/L), MCV (105) and Alkaline Phosphate (120 U/L) above normal limits LDH (101) and platelets (100x103/mm3) are below normal limits

Assessment: The patient developed liver damage due to excessive alcohol use. It also caused a false positive result for thrombocytopenia which decreases her platelets. Plan: o practical counseling (problem-solving/skills training) o social support (family members) o stress management o relapse prevention

6. Anemia
Objectives: in Folate, Hct, Hgb, MCV

Assessment:
patient has megaloblastic anemia evidenced by

folate and MCV aggravated by alcoholism

Plan:
Non Pharmacological Treatment eat green leafy vegetables Food rich in iron Pharmacological Treatment take iron supplement like Folic acid (Folart) 5mg PO OD

7. Smoking
Subjective: (+) 22pack/year history Assessment: The patient was having 22 pack/year of cigarette which contributed to development of Osteoporosis. Smoking decreases the Bone Mass Density and increases fracture risk. Plan: o practical counseling (problem-solving/skills training) o social support (especially family members) o stress management o relapse prevention

1. What percentage range of spinal bone loss must occur in TF for detection of osteoporosis by routine spinal radiography?

Answer

: 20-40%

2.Describe the mechanism of action of the pharmacologic and nonpharmacologic interventions employed in the treatment of osteoporosis in this case.

A: Biphosphonates which inhibits bone resorption via actions on osteoclasts or osteoclasts precursors; decreases the rate of bone resorption, leading to an indirect increase in bone mineral density.

3.According to the National Institutes of Health, what is the recommended daily calcium intake of TF?

Answer: Daily calcium intake of age 51-70 is 1200mg

4. Which calcium salt would provide TF with the highest percentage of elemental calcium? Answer:

Calcium Carbonate has 40% elemental calcium

5. What therapeutic options might be useful in TF for its analgesic effect on the back pain associated with osteoporosis vertebral fractures?

Answer: Calcitonin Narcotic Pain Reliever NSAID Acetaminophen

6. Which of the following risks of hormone replacement therapy (estrogen with progestin) should be discussed with TF? Answer: Development of breast and uterine cancer Heart Attack Stroke Alzheimers Disease Dementia

7. Describe benefits of estrogen therapy other than prevention of osteoporosis that should be discussed with TF? Answer: Prevention and controlling menopausal symptoms, decreased vertebral, hip and all fractures by 34%, 34%, and 24% respectively.

8.During her past three visit to outpatient clinic, TFs blood pressure has measured 140/85, 142/90 and 148/90 respectively, what would be an appropriate choice for treatment of hypertension in a patient with osteoporosis? Answer: Angiotensin-Converting-Enzyme Inhibitors can be used for the treatment of hypertension in patient with osteoporosis due to less side effects.