Osteoporosis Flashcards
Bone resorption
removal of Ca and removal of old damaged bone tissue (osteoclasts) leaving small spaces
Bone formation
use Ca and P to fill spaces with new bones
Why does bone remodeling occur?
adjust bone according to mechanical strain, repair microfactures, provide access to mineral stores
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
Mineralization occurs mostly with
CaPO4 deposition and requires the presence of vit D
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
Normalization of Ca results in a negative feedback signal causing
decreased release of PTH
Recommended amount of Calcium and Vit D in the diet (19-30 yo)
1000 mg/d and 600 IU/d
Calcitonin
made in thyroid gland and has major effect on bone, released when [Ca] increases and acts to inhibit bone breakdown and lower [Ca]
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
Glucocorticoids
necessary for skeletal growth, excess steroid decrease Ca reabsorption and stimulate PTH secretion, causes bone loss
Adrogens and estrogens
result in diminished bone turnover rate, inhibiting osteoclast activity and increasing osteoblast activity. Estrogen causes Ca retention
Mechanism of osteoporosis
imbalance between rate of resorption and formation
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
Osteoporosis presentation
decrease ht, bent over, change in spine, slow gait, wide stance, clothes do not fit, crowding of internal organs
Non pharm approaches for osteoporosis
low calcium and vit D, fall prevention, exercise, smoking cessation, avoid alcohol
Calcium MOA
inhibit bone resorption to reduce bone loss, increase bone mass and reduce fx, increase bone mineral density
How to take calcium
take 1 tab TID with meals, not 3 tabs at once, vit D is required for absorption
ADRs of calcium
constipation, flatulence, upset stomach
Drug interactions with calcium
Ca is a clelator, problematic with antibiotics
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
