Endocrine Module Flashcards
Osteoporosis
Systemic skeletal disorder characterized by decreased bone mass density leading to diminished stature, bone fragility, increased risk of bone fracture
After what age in women do bone strength and density begin to decline?
35
What fraction of men/women have osteoporosis?
1/4 women
1/8 men
Where is the body’s calcium located?
99% in teeth and bones
1% in extracellular fluid and soft tissue
Metabolic processes calcium is involved in
Cell membrane function and permeability
Neuronal excitability and transmission of electrical impulses
Contraction of muscle
Conduction of electrical impulses in the heart
Blood coagulation
Platelet adhesion
Hormone secretion
Enzymatic activity
Catecholamine release from adrenal medulla
Release of chemical mediators
Bone
Mineralized connective tissue that provides structural support and acts as reservoir for calcium, phosphorus, magnesium, sodium, carbonate
Two main forms of calcium in bone tissue
Calcium phosphate
Calcium carbonate
A small amount exists in an unbound, unionized form that moves from bone to bloodstream when serum calcium is low
What % of consumed calcium is absorbed in the intestine?
30-50% - the rest is lost in feces
Absorption of calcium is increased by
Presence of vitamin D, lactose, moderate amounts of fat, high protein intake, physiologic need
Absorption of calcium is impaired with
Vitamin D deficiency, high fat diet, diarrhea
How much calcium should adults consume?
1000 mg/day
How much calcium should growing children, pregnant/lactating women and postmenopausal women (no HRT) consume?
1200 mg/day
What is the best source of calcium?
Milk and milk products (also contain vitamin D and lactose which increase calcium absorption)
What are good sources of calcium besides milk?
Broccoli, spinach, kale, shellfish such as clams and oysters
Which 3 hormones regulate calcium and bone metabolism?
Parathyroid hormone
Calcitonin
Calcitriol
Parathyroid hormone
Secreted from parathyroid gland when serum calcium falls
Stimulates activity of osteoclasts to increase bone resorption
Increases reabsorption of calcium in tubules of kidneys
Activates calcitriol (active form of vitamin D) in the intestines
Calcitonin
Secreted from thyroid gland when serum calcium rises
Inhibits activity of osteoclasts to stimulate rate of deposition
Inhibits reabsorption of calcium in tubules of kidneys to increase amount excreted in urine
2 forms of vitamin D
Ergo-calciferol obtained from diet
Cholecalciferol - synthesized from cholesterol in skin when exposed to UV light
Calcifediol
Intermediate metabolite of vitamin D (formed in liver)
Calcitriol
Active form of vitamin D (formed in kidneys)
Enhances intestinal absorption of calcium
2 types of receptors calcitriol works on
- Membrane level - activates L-type calcium channels to modulate calcium influx across cell borders
- Intracellular protein - calcitriol protein complex enters nucleus and causes nuclear DNA to generate an mRNA specific for production of a calcium binding protein that intermediates in the system effects of calcitriol
Action of calcitriol at the tissue/system level
Stimulates intestinal calcium and phosphate transport
Increases serum calcium and phosphate from bone resorption through inducing differentiation of osteoclasts
Decreases renal excretion of calcium and phosphate
What is indicative of undetected osteoporosis?
Shortened stature
Back pain
Spinal deformity
Causes of osteoporosis
Inadequate dietary calcium
Inadequate calcium absorption
Vitamin D deficiency
Disruption of calcium and bone metabolism (hypersecretion of PTH, hyposecretion of calcitonin)
Which body areas are particularly vulnerable to osteoporosis related fracture?
Vertebrae of lower dorsal and lumbar spines
Wrists
Hips
When to osteoporotic fractures often occur?
After bending or lifting movements, slips, trips, falls
Alterable/minor risk factors
- Smoking - increases calcium excretion via kidneys
- Calcium and vitamin D deficiency - increases bone resorption
- Increased sodium or protein intake - increases calcium excretion via kidneys and increases bone resorption
- Caffeine and alcohol - cause diuresis leading to increased calcium excretion
- Lack of exercise - exercise helps retain calcium and increases bone mass density
Major risk factors
Female gender (esp. with advanced age, prolonged amenorrhea, menopause because estradiol limits activity of osteoclasts and progesterone stimulates osteoblasts to build new bone)
Fragility fractures (less than 40 y/o)
Ancestry - Asian or Caucasian
Small frame - smaller bones, less mass
Family history - especially maternal
Glucocorticoid therapy for more than 3 months - inhibits bone deposition and increases resorption
Who should be assessed for presence of risk factors for osteoporosis?
All adults over 50
Anyone over 50 should undergo bone mass density testing if…
They are over 65 Fragility fractures after age 40 Family history of osteoporotic fracture Use of high dose systemic glucocorticoid therapy for 3 months Current smoking or alcohol Low body weight Rheumatoid arthritis
Anyone under 50 should undergo bone mass density testing if…
History of fragility fractures
Premature menopause
Primary hyperparathyroidism
Hypogonadism
How are bone mass density tests performed?
Dual energy x-ray absorptionmetry
Test scans lumbar region and one hip
Takes about 10 minutes
Low radiation exposure, high sensitivity for diagnosis
If bone mass density is normal and they are deemed low risk for fracture…
Repeated testing every 5 years
Recommended calcium/vitamin D intake for postmenopausal women
1200 mg calcium
800-2000 IU vitamin D
If a client is deemed moderate risk for fracture…
Preventative strategies such as lifestyle change and pharmacotherapy initiated
In cases of severe bone mass density loss…
Pharmacological treatment for osteoporosis is required to increase bone mass density and mediate high risk of fragility fracture
In cases of moderate/high risk for fracture…
Bone mass density tests every 1-3 years
Recommended calcium/vitamin D intake for people with osteoporosis
1000 mg/day calcium
800 IU/day vitamin D
Insufficient to prevent fracture, used as adjunct
Pharmacological treatment option
Hormone replacement therapy Selective estrogen receptor modulators Bisphosphonates RANKL inhibitors Parathyroid hormone
Hormone therapy
Estrogen and progesterone which have a positive effect on bone mass density - prevents loss in menopausal women and increase density in patients with existing osteoporosis
Who is HRT recommended in?
Women with moderate-severe symptoms due to risk of breast cancer, heart disease, stroke - hot flashes, night sweats, disrupted sleep pattern, fatigue
HRT should not be prescribed for
Solely for treatment of osteoporosis
Routes of admin for HRT
Oral and transdermal
Selective estrogen receptor modulators
Act as an estrogen agonist at beta-estrogen receptors in bone to inhibit osteoclast activity and reduce rate of bone resorption
Act as an estrogen antagonist at alpha-estrogen receptors in breast and endometrial tissue - no risk of breast or uterine cancer
What are SERMs recommended for?
Prevention and treatment in asymptomatic menopausal and post-menopausal women
Adverse effects of SERMs
Leg cramps
Hot flashes
Venous thromboembolism
Tissue selective estrogen complexes
Combine SERMs with one or more synthetic estrogens, effective for relief of menopausal symptoms and prevention of bone loss
Protect breast and endometrium from oncogenic effects of unopposed estrogen
What are TSECs recommended for?
Prevention of postmenopausal osteoporosis
Bisphosphonates
Drug class of choice to prevent and treat osteoporosis Inhibit osteoclast activity and reduce bone resorption, increase bone mass density and overall bone strength
How soon are results seen in bisphosphonate therapy?
1-3 months
How should alendronate and risedronate be administered
Orally, daily
Empty stomach with full glass of water to minimize risk of esophageal irritation and improve absorption
No other food or meds 30 minutes post-admin and remain upright
Adverse effects related to abdominal pain and dysphagia
Most potent bisphosphonate
Zoledronic acid
How should zoledronic acid be administered and for what scenario?
IV annually for treatment of postmenopausal osteoporosis
Less frequent dosing (increased adherence) and reduced risk of GI effects
Atypical femur fractures are associated with
Long term use of bisphosphonates (5-7 years)
AFFs are often preceded by
Pain in thigh or groin weeks-months before fractuer
If clients report pain in thigh or groin, what tests should be performed and why?
AFF risk - radiography, bone scans, MRI
If any evidence of AFF is present…
Bisphosphonate therapy should be discontinued
Drug holidays from long term bisphosphonate therapy
Reduce AFF risk
Long term skeletal retention and stable bone mass density are shown after how many years of bisphosphonate therapy?
5
Discontinuation after 5 years of bisphosphonate therapy is appropriate for…
Those at moderate risk of fracture
In high risk, benefit of continuation of therapy outweighs risks
How are bisphosphonates cleared?
Renally - only 50% is deposited in bone
What is the drug of choice with renal dysfunction?
Denosumab
Receptor activator of nuclear factor kappa-B ligand inhibitors
RANKL - binds to RANK receptor on osteoclasts to promote removal of calcium from bone
Estrogen deficiency stimulates upregulation of RANKL, increasing osteoclast function
How are RANKLs administered?
SC injection twice yearly
First drug of choice in postmenopausal women at high risk of fracture or in those that do not tolerate or respond to bisphosphonate therapy
RANKL inhibitors
Clients taking RANKL inhibitors should seek medical attention for
Signs of infection
Allergic reaction
Skin damage
AFF
Common adverse effects of RANKL inhibitors
Hypocalcemia, fatigue, GI disturbance, MSK pain, skin lesions, increased risk for infection
Increased risk for AFF
Parathyroid hormone (teriparatide)
Builds new bone
PTH is recommended for use in…
Cases of severe osteoporosis or those who do not respond to other treatments
How is PTH administered?
Daily SC for no longer than 24 months - osteosarcoma risk
Intermittent administration increases osteoblast activity and promotes deposition
What adverse effects are associated with PTH therapy?
Nausea, dizziness, leg cramps
Antiresorptive therapies include
HRT
Bisphosphonates
SERMs
Calcitonin
Is combination resorptive therapy recommended?
No
Risk of hip fracture compared to breast cancer
1/6 fracture hip, 1/9 develop breast cancer
Death rate for hip fracture is higher
Long term effects of hip fracture
50% do not return to previous functional state
20% require LTC
