metabolic conditions

what is osteoporosis?

most common metabolic disease of the skeleton

how does osteoporosis occur?

occurs when rate of bone resorption is greater than bone formation

osteoporosis pathogenesis

trabeculae at the core becomes less dense, cortical bone on the perimeter loses thickness (bones are brittle and porous)

• width and bone mass decreased; fragile bone fractures easily

• cancellous bone is lost faster than cortical bone

diagnostics of osteoporosis

osteopenia: low bone mineral density (BMD)

dual-energy X-ray absorptiometry (DXA) XR and CT scan show vertebrae injuries

may have elevated PTH

causes and risk factors: estrogen deficiency

deficiency of estrogen increases bone resorption, caused by increased OC numbers (due to enhanced OC formation and reduced OC apoptosis)

causes and risk factors: insufficient calcium

serum calcium is tightly regulated by vitamin D and PTH

leads to secondary hyperparathyroidism, which increases the rate of bone remodeling to main calcium homeostasis

imbalance between resorption and formation of bone leads to accelerated bone tissue loss

causes and risk factors: vitamin D deficiency

leads to secondary hyperparathyroidism and accelerated bone loss

at risk populations:

• obesity

• people that live far from the equator

• elderly

causes and risk factors: physical inactivity

inactivity results in minimal strain and shift in bone remodeling toward osteoclast activity, leading to bone loss

causes and risk factors: smoking

tobacco compounds have a direct toxic effect of osteoblasts

estrogen metabolism is altered, leading to earlier menopause

smokers are more likely to have poor exercise habits and a need for medications that may be detrimental to bone health (e.g. glucocorticoids for lung disease)

causes and risk factors: diseases and disorders

certain GI diseases result in impaired absorption of Ca, Phos, and vitamin D

endocrine disorders can impair bone health through a variety of mechanisms

in hypogonadal states, there is decreased functional activity of the gonads and the positive effects of estrogen on bone health is reduced

medications: glucocorticoids and immunosuppressants

stimulation of osteoclast differentiation

inhibition of osteoblast proliferation

decrease in intestinal calcium absorption

most common Rx: Prednisone and Cyclosporine

medications: thyroid hormone

directly stimulate bone resorption

endogenous thyrotoxicosis accelerates bone turnover → significant risk factor for OP

medications: aromatase inhibtors

used for treatment of estrogen-dependent cancer of the breast and ovaries

limit the synthesis of estrogen → bone loss secondary to estrogen deficiency

s/s of osteoporosis

shortened stature

muscle wasting

back muscle spasms

difficulty bending over

humped back

recurrent fracture of vertebrae, femur, and/or distal radius

tx options for osteoporosis

exercise

heat

calcium and vitamin D supplements

bisphosphonates

recombinant human parathyroid hormone

osteoporosis prevention

diet and exercise

risk reduction

rx osteoporosis

calcium availability

osteoblast promotion

osteoclast inhibition

examples of calcium supplements

tums (calcium carbonate)

calcitrate (best absorbed)

OsCal

dosage for calcium supplements

dosage: 1200 mg for F > 50y

cannot take more than 600 mg each dose, take BID or 400 mg TID

adverse effects of calcium supplements

interactions with some drugs

hypercalcemia with chronic high doses

vitamin D importance

necessary for Ca absorption

sources of vitamin D

sunlight

cod liver oil

trout

salmon

mushrooms

fortified milk/juice/cereals

eggs

tuna

sardines

dietary supplements

PTH replacement rx example

teriparatide (Forteo): subcutaneous injection

PTH replacement rx purpose

when given intermittently, promotes bone formation via:

increased vitamin D production

increased Ca reabsorption in kidneys

increased osteoblast activity

calcitonin rx examples

Miaclacin, Calcimar

• injection or nasal spray

what is calcitonin used for?

treatment of osteoporosis, but not prevention

hypercalcemia

bisphosphonates action

inhibits osteoclast-mediated bone resorption

• indirectly enhances bone mineral density

strong clinical evidence indicates bisphosphonates can reverse bone mass and reduce fracture risk

bisphosphonates dosage

multiple reparations available (daily, weekly, or monthly dose)

• adverse effects include esophagitis

selective estrogen receptor modifiers (SERM)

indicated for postmenopausal osteoporosis

• Raloxifene (Evista)

• Tamoxifen (Nolvadex)

added benefits of selective estrogen receptor modifiers (SERM)

reduced breast cancer

improve cholesterol by reducing LDL

what is rickets and osteomalacia?

bone growth condition due to vitamin deficiency

what is rickets?

defective mineralization of the growth plate

primarily seen in children

what is is osteomalacia?

defective mineralization of the preformed osteoid

may occur at any age

etiology of rickets and osteomalacia

lack of appropriate bone-building material due to:

• inadequate concentration of vitamin D, calcium, or phosphorus

• poor vitamin D metabolism

• renal disease

leads to inadequate or delayed mineralization of bone → soft, weak bone tissue

s/s of rickets and osteomalacia

bone pain (especially pelvis)

pathologic fractures

muscle weakness

low calcium symptoms

tx options for rickets and osteomalacia

ergocalciferol as a vitamin D supplement

phosphate supplement

calcium supplement