Osteoporosis Flashcards by Lisa Letterman

Bone resorption

removal of Ca and removal of old damaged bone tissue (osteoclasts) leaving small spaces

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Bone formation

use Ca and P to fill spaces with new bones

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Why does bone remodeling occur?

adjust bone according to mechanical strain, repair microfactures, provide access to mineral stores

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How is bone remodeling regulated?

initiated by osteocytes (identify damage), sends signals to stimulate osteoclasts, secretes collagenases and proteinases, resorb bone matrix and release Ca, osteoblast begin formation, bone is mineralized

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Mineralization occurs mostly with

CaPO4 deposition and requires the presence of vit D

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3 functions of parathyroid hormone

increase renal Ca reabsorption and phosphate excretion, promote bone resorption to release Ca from bone, result in conversion of 25 hydroxyvit D to active metabolite be activating an enzyme in the kidney

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Normalization of Ca results in a negative feedback signal causing

decreased release of PTH

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Recommended amount of Calcium and Vit D in the diet (19-30 yo)

1000 mg/d and 600 IU/d

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Calcitonin

made in thyroid gland and has major effect on bone, released when [Ca] increases and acts to inhibit bone breakdown and lower [Ca]

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How does Calcitonin decrease plasma Ca levels

it is an antagonist to PTH, stimulated by increase in plasma Ca levels, target cell is the osteoclast, inhibits osteoclasts with rapid decrease in Ca caused by inhibition of bone resorption

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Glucocorticoids

necessary for skeletal growth, excess steroid decrease Ca reabsorption and stimulate PTH secretion, causes bone loss

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Adrogens and estrogens

result in diminished bone turnover rate, inhibiting osteoclast activity and increasing osteoblast activity. Estrogen causes Ca retention

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Mechanism of osteoporosis

imbalance between rate of resorption and formation

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Osteoporosis risk factors

gender, ethnicity, body composition, fam hx of osteoporosis, RA, thyroid/liver disease, spinal cord injury, physical activity level, low Ca, lifestyle habits, recurrent falls, smoking, thyroid replacement, coricosteroids, antacids, long term anti-convulsant use

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Osteoporosis presentation

decrease ht, bent over, change in spine, slow gait, wide stance, clothes do not fit, crowding of internal organs

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Non pharm approaches for osteoporosis

low calcium and vit D, fall prevention, exercise, smoking cessation, avoid alcohol

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Calcium MOA

inhibit bone resorption to reduce bone loss, increase bone mass and reduce fx, increase bone mineral density

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How to take calcium

take 1 tab TID with meals, not 3 tabs at once, vit D is required for absorption

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ADRs of calcium

constipation, flatulence, upset stomach

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Drug interactions with calcium

Ca is a clelator, problematic with antibiotics

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Bisphosphonates

Alendronate (Fosamax), Ibandronate (Boniva), Risedronate (Actonel), Zoledronic acid (Reclast), Pamidronate (Aredia), Tiludronate (skelid), Clondronate, Etidronate

Bisphosphanates MOA

inhibit bone resorption by binding to bone mineral surface, are taken up by osteoclast and induce osteoclast apoptosis, decreases [Ca] and [Phos]

Clinical use of bisphosphonates

osteoporosis, hypercalcemia of malignancy, Paget’s disease, metastatic bone disease due to breast cancer, multiple myeloma, osteolytic bone lesions

Pharmocokinetics of bisphosphonates

IV and PO, compromised with coffee/juice, avoid in pts w/ CrCl,30 ml/min, very long half life

Contraindications

hypocalcemia, esophageal abnormalities delay esophageal emptying

ADRs of bisphosphonates

fatigue, HA, insomnia, hypocalcemia, GI mucosa irritation, erosions, esophagitis, ulcers, dysphagia, osteonecrosis of the jaw

How to combat GI adr in bisphosphonates

pt should take first thing in the morn, 30 min before breakfast and glass of plain water, remain upright 30 min after administration

Alendronate (Fosamax)

first one marketed, 10 year T1/2, PO only, once a week, given daily sometimes, less expensive

Ibandronate (Boniva)

T1/2 37-157 hours, PO given once monthly, coated tablet (decrease GI irritation), IV given every 3 months

Risedronate (Actonel)

T1/2 480-561 hours, coat tablet (decrease GI irritaton), IV, once weekly or monthly

Zoledronic acid

reclast- ostroporosis (given once a year), Zometa- all other indications, largely onc related, T1/2 146 hours, suspected to be nephrotoxic, only available IV

Pamidronate (Aredia)

not for osteoporosis, only hypercalcemia, paget's and onc related uses, T1/2: 21-35 hours, IV, only one with data for use in renal failure

Conjugated estrogen (Premarin) MOA

inhibits bone resorption, often considered most efficacious but patient selectionis critically important due to ADR profile, PO and transdermal patch

Clinical use of conjugated estrogen (Premarin)

menopause symptoms, Prevention of postmenopausal osteoporosis in high risk women, low estrogen, and others

Contraindications in estrogen

genital bleeding, Br CA, estrogen-dependent malignancy, VTE, arterial thromboembolic disease, pregnancy

ADRs of estrogen

increased risk of CV events, HTN, MI, stroke, pulmonary emboli, DVT, DC 4-6 weeks prior to surgeries, CV risk w/ estrogen remains controversial, increased risk of Br CA, dementia, nausea, HA, edema, migraines, endometrial CA

Things to consider before starting estrogen

menopausal sx, osteoporosis risk, CVD risk, Br Ca risk, thromboembolic risk, dementia risk

Estrogen receptor modulators

Ralocifene (Evista)

MOA of Ralocifene (Evista)

non-hormonal agent which inhibits bone resorption similar to estrogen, very specific to bone, antagonist to breast and uterus

Ralocifene (Evista) clinical use

prevention or treatment of osteoporosis, prevention of br CA in high risk pts, PO, chronic therapy

Ralocifene (Evista) contraindications

active or past h/o VTE, lactating/ pregnancy

Ralocifene (Evista) ADRs

hot flashes, wt gain, edema, decrease LDL, decreased endometrial activity, decrease risk of breast CA

Calcitonin (Calcimar)

subcut or IM injection

Salmon-calcitonin (Miacalcin)

nasal spray

Calcitonin MOA

inhibit osteoclastic bone resorption, 10 x more potent than endogenous calcitonin, has analgesic properties

Calcitonin clinical uses

osteoporosis (Miacalcin) for pt who can't take bisphosphonates, hypercalcemia (calcimar), off label for pain control for bone metastasis

Calcitonin ADRs

intranasal- rhinitis, epistaxis, dryness, nasal irritation, Subcut: flushing, nausea, injection site reaction

Teriparatide (Forteo) MOA

recombinant PTH, principal regulator of Ca, increases/stimulates osteoblast function, once daily, $$$

Teriparatide (Forteo) clinical uses

reserved for failures of antiresorptive therapy, treatment of postmenopausal osteoporosis, increase BMD in men w. osteoporosis associated with hypogonadism

Teriparatide (Forteo) ADRs and contraindications

postural hypotension and several