Week 13 - Osteoporosis Flashcards
How many women will have an osteoporotic fracture in their lifetime?
1/3
How many men will have an osteoporotic fracture in their lifetime?
1/5
__% of all fractures (>50yo) = d/t osteoporosis
80%
__% of women and __% men will die within following year of hip fracture
28% women
37% men
Osteoporotic fracture DDX
malignancy primary hyperparathyroidism osteomalacia Paget's disease osteogenesis imperfecta
define hyperparathyroidism
Hyperparathyroidism is overactivity of the parathyroid glands resulting in excess production of parathyroid hormone (PTH). The parathyroid hormone regulates calcium and phosphate levels and helps to maintain these levels. Excessive PTH secretion may be due to problems in the glands themselves, in which case it is referred to as primary hyperparathyroidism and which leads to hypercalcaemia (raised calcium levels). It may also occur in response to low calcium levels, as encountered in various situations such as vitamin D deficiency or chronic kidney disease; this is referred to as secondary hyperparathyroidism. In all cases, the raised PTH levels are harmful to bone, and treatment is often needed.
define Paget’s disease
A chronic disorder that can result in enlarged and misshapen bones. Paget’s is caused by the excessive breakdown and formation of bone, followed by disorganized bone remodelling. This causes affected bone to weaken, resulting in pain, misshapen bones, fractures and arthritis in the joints near the affected bones. Rarely, it can develop into a primary bone cancer known as Paget’s sarcoma. Often Paget’s disease is localized to only a few bones in the body. The pelvis, femur, and lower lumbar vertebrae are the most commonly affected bones.
What is the action of PTH - parathyroid hormone
Parathyroid hormone (PTH), parathormone or parathyrin, is secreted by the chief cells of the parathyroid glands as a polypeptide containing 84 amino acids. It acts to increase the concentration of calcium (Ca2+) in the blood, whereas calcitonin (a hormone produced by the parafollicular cells (C cells) of the thyroid gland) acts to decrease calcium concentration. PTH acts to increase the concentration of calcium in the blood by acting upon the parathyroid hormone 1 receptor (high levels in bone and kidney) and the parathyroid hormone 2 receptor (high levels in the central nervous system, pancreas, testis, and placenta). PTH half-life is approximately 4 minutes.
Define osteoporosis
- skeletal SYSTEMIC disorder
- low bone mass
- microarchitectural deterioration of bone
- increased incidence of fragility fractures
Dx tests for osteoporosis
BMD via DEXA scan CBC (nutrition/myeloma) TSH (hypothyroid) Vitamin D calcium albumin creatinine alkaline phosphatase
What is the BMD cutoff below mean for dx osteoporosis?
Spinal/hip bone mineral density (BMD) of 2.5 standard deviation (or more) below mean for healthy, young adult as per duel energy x-ray absorptionmetry (DEXA)
What is the SD value criterion for Osteopenia
1-2.5 SD
What is the SD value criterion for severe osteoporosis
> 2.5 + fragility fracture
What is the SD value criterion for normal
<1 SD
What is a “fragility fracture”
occurs spontaneously or following minor trauma (fall from standing height or less)
High risk medications for development of osteoporosis
- corticosteroids
- PPIs
- thiazolidinedione
- aromatase inhibitors
- anticonvulsants
- anticoagulants
- SSRIs
Type I primary osteoporosis criteria: age
51-75 yo
Type I primary osteoporosis criteria: what kind of bone loss
trabecular
Type I primary osteoporosis criteria: what kind of fracture
vertebral body & forearm fractures
Type II primary osteoporosis criteria: age
> 75yo
Type I primary osteoporosis criteria: what kind of bone loss
trabecular & cortical bone loss
Type I primary osteoporosis criteria: what kind of fractures
femoral neck, pelvis, humerus, tibia
secondary osteoporosis d/t?
nutritional deficiencies
chronic illness
exposures
etc.
Would you screen a male 70yo for osteoporosis?
Yes
screen all people >65yo regardless of health status
Would you screen a female 63 yo for osteoporosis?
yes screen WOMEN 50-64yo if: - fragility fracture after 40yo - glucocorticoids - high risk medication - parental hip fracture - vertebral fracture/osteopenia - current smoking - high alcohol intake - low body weight/wt loss - RA - other at risk conditions (hyperparathyroid, DM I, premature menopause, etc.)
Would you screen a 44 yo male smoker for osteoporosis?
no.
screen all people <50yo only if:
- fragility fracture
- glucocorticoids
- high risk medications
- hypogonadism/premature menopause
- malabsorption
- primary hyperparathyroidism
- other (rapid bone loss/fracture)
Would you screen a 50 yo woman who has never had a fracture, is not taking any medication, is a current smoker, and has no medical conditions?
yes - current smoker
screen WOMEN 50-64yo if:
- fragility fracture after 40yo
- glucocorticoids
- high risk medication
- parental hip fracture
- vertebral fracture/osteopenia
- current smoking
- high alcohol intake
- low body weight/wt loss
- RA
- other at risk conditions (hyperparathyroid, DM I, premature menopause, etc.)
Would you screen a 42 year old male who has been using a cortisone cream for over a year?
Yes - glucocorticoid medication
screen all people <50yo only if:
- fragility fracture
- glucocorticoids
- high risk medications
- hypogonadism/premature menopause
- malabsorption
- primary hyperparathyroidism
- other (rapid bone loss/fracture)
What is the relationship between genetics and osteoporosis?
- genetics contributes to 50-85% of cases
- heritability independent of BMD!
- related genes:
collagen type 1
vitamin D receptor
estrogen receptor
lipoprotein receptor protein 5 & 6
IL-6
What are estrogen’s effects on bone?
The major physiological effect of estrogen is to inhibit bone resorption.
Estrogen effects may be mediated in part by growth factors and interleukins. For example, interleukin 6 is a potent stimulator of bone resorption, and estrogen blocks the osteoblast’s synthesis of interleukin 6. Estrogen may also antagonize the interleukin 6 receptors.
Osteoclast apoptosis is regulated by estrogens. With estrogen deficiency, the osteoclasts live longer and are therefore able to resorb more bone. In response to the increased bone resorption, there is increased bone formation and a high-turnover state develops which leads to bone loss and perforation of the trabecular plates.
Osteoclast apoptosis is regulated by ______.
Osteoclast apoptosis is regulated by estrogens.
What is the effect of thyroid hormones on bone metabolism?
Thyroid hormones are essential for normal skeletal growth and the maintenance of bone mass in adulthood, although their mechanism of action in bone is poorly understood. Hypothyroidism causes impaired bone formation and growth retardation whereas thyrotoxicosis results in accelerated growth, advanced bone age and decreased bone mass. Adults with thyrotoxicosis or a suppressed thyroid stimulating hormone (TSH) from any cause have an increased risk of osteoporotic fracture.
Current USPSTF recommendation for Calcium in osteoporosis?
“The UPSTF recommends against daily supplementation with 400 IU or less of vitamin D3 and 1000mg or less of calcium for the primary prevention of fracture in non-institutionalized postmenopausal women.”
Statement does not apply to: institutionalized patients pts w osteoporosis hx of fractures vit D deficiency
what is the link bw calcium supplementation and cardiovascular risk?
- Calcium supplements ↑ risk of MI by 27-31%
- Calcium/CaD ↑ the risk of myocardial infarction by 24-26% and stroke by 15-19%
- 5 years; will cause 6 MI out of 1000 people, and prevent 3 fractures
Adverse effects of calcium supplementation
- nausea, dyspepsia, constipation
- nephrolithiasis
- CV risk
↑ undercarboxylated (inactive) osteocalcin may result from subclinical vitamin ___ deficiency – seen in elderly
↑ undercarboxylated (inactive) osteocalcin may result from subclinical vitamin K deficiency – seen in elderly
Inverse association b/w vitamin __ (circulation levels, intake,↑uncarboxylated osteocalcin) and fracture risk
Inverse association b/w vitamin K (circulation levels, intake,↑uncarboxylated osteocalcin) and fracture risk
Osteoporosis Canada recommendation for Vitamin D in osteoporosis
400-1000 IU for 50yo
Relationship bw protein intake & osteoporosis
Low calcium intake: slight increase fractures
High protein: no impact on fractures
High protein + low calcium: increase fractures
Is there a Relation bw coffee consumption & osteoporosis?
No!
≥4 cups/d, compared to <0.001) lower BMD lumbar spine
2% ↓ lower BMD proximal femur
“Theoretically, the small decrease in BMD associated with high coffee consumption might be counteracted by a reduced likelihood of hypotension and co-morbidities leading to a lower propensity for injurious falls.”
Osteogenic potential of exercise is dependent on?
Osteogenic potential of exercise is dependent on: (Gunter 2012) Magnitude of load Rate at which it is applied Duration of loading Novel nature of load
define sarcopenia
Sarcopenia (from Greek σάρξ sarx, “flesh” and πενία penia, “poverty”) is the degenerative loss of skeletal muscle mass (0.5–1% loss per year after the age of 25), quality, and strength associated with aging. Sarcopenia is a component of the frailty syndrome. It can be differentiated from cachexia in that cachexia includes malaise and is secondary to an underlying pathosis (such as cancer), whereas sarcopenia may occur in healthy people and does not necessarily include malaise.
What are bisphosphonates
Bisphosphonates are a class of drugs that prevent the loss of bone mass, used to treat osteoporosis and similar diseases. They are the most commonly prescribed drugs used to treat osteoporosis. They are called bisphosphonates because they have two phosphonate (PO 3) groups.
Analog to pyrophosphate.
Binds to hydroxyapatite.
Removed by osteoclasts during resorption but don’t get excreted. (stay for 10 yrs in the skeleton)
Prevent osteoclast function, leading to decreased bone turnover leading to osteoclast apoptosis.
Oral bisphosphonates are poorly absorbed (less than 1%), and the dose has to be administered with plain water only, after an overnight fast, and followed by 30-60 minutes without eating or drinking. The patients need to stand upright for one hour to prevent gastroesophageal reflux and damage to the mucosa
- Concern that long-term treatment has the potential to oversuppress bone remodeling and inhibit repair of microdamage, cause excessive mineralization, and cause an increase in micro cracks.
Impact of soy on osteoporosis?
↑ BMD by 54% vs. placebo (p<0.001)
↓ bone resorption makers by 25% vs. baseline
Greater impact with dose ≥75mg/d
Bot med w/preclinical data
Withania somnifera
Promotes osteoblastogenesis + suppresses osteoclast differentiation, ↑ bone strength, ↓ bone turnover markers (in vitro + animal)
Panax ginseng
Bone modulating capacity (in vitro)
↓ Ca2+ urinary excretion, ↑ bone strength (animal study)
