Osteoporosis & Pagets Disease Flashcards
What is Osteoporosis
what is osteopenia
Osteoporosis
- a condition which is loss of the bone matrix (the middle, not the hard bone outside)
- results in decreased integrity and strength of the bone
- results in risk of frature and fragility
- BMD measurement at Any site that is 2.5 SD below the young adult standard
- normally: made as a clinical diagnosis with an at risk pt. then you test and find out they have it
Osteopenia
- T-score < -1 but > -2.5
- T score = bone density in comparison to a young, helathy individual of the same sex
Bone Physiology
Bone Remodeling
Physiology
- bones are active structures which continuous change over time with wear/tear
- Bone Remodeling: skeletal cahnges of resorbtion of old bone and deposition of new
Bone Remodeling
- a normal repair process which renews small defects from normal wear/teat
- maintains normal vasculature and levels of calcium and phosphate in the body
- the rate of new bone formation = the rate of bone resorbtion (breakdown)
Influenced by…
- osteoclasts
- osteoblasts
- osteocytes
- parathyroid hormone
- Vit D
- Estrogen
- calcitonin
- growth hormone
- glucocorticoids
- thyroid
Bone Modeling (pathologic)
- Imbalance between osteblastic and osteoclastic activity that results in
- decreased bone mass due to overwokring osteoclasts
- increase bone mass in areas where there is increased load on the skeleton to pull
Bone Remodeling Phases
- resting/quiescence
- resorbtion: osteoclast activity breaks apart and released calcium
- reversal: osteoblasts replace the oestoclasts
- mineralization: buidl up of bon eby osteoblasts
Pathogenesis of Osteoporosis
3 mechanisms
Mechanisms
Estrogen Deficiency (why we see this in post-menopausal women)
- estrogen loss leads to bone modeling (wehre clasts»_space; blasts) resulting in decreased bone mass
- influences the local action of Blasts & Clasts
- blocks Il-6
- osteoclasts work better in decreased estrogen state
Calcium/Vit D deficiency which results in secondary hyperparathyroidism and bone breakdown
Parathyroid Hormone
- acts to raise blood calcium levels by acting directly on bones, kidneys and intestines
- a negative feedback: low calcium stimulates PTH release
- PTH acts on osteoclasts through RANKL system to increae theri activity and increase calcium release
Vitamin D
- insuf = 12-20, defi. = < 12
- can be a reuslt of low sun expsoure, aging and decreased ability to convert Vit D2 to Vit D3
- lack of Vit D leads to lack of calcium aborbition
- results in accelerated bone loss, muscle weakness adn falls = fratures
Hormonal influences in men (hypogonadism)
- androgens determine the peak bone health in men
- this gradually falls with age
- in severe hypogonadism men can get OP
Role of … in OP
- Calcitonin
- Growth Hormone
- Glucocorticoids
- Thyroid Hormone
Calcitonin
- produced by C cells in thyroid: respond to elevated calcium levels
- bind to the osteoclasts and inhibit their ability to breakdown bown for resporbtion
- not used much as target for trreatment, but there is one med
Growth Hormone
- acts through IGF-1 to inihibti bone resorbtion and stimulate bone formation
Glucocorticoids
- decreased bone formation by favoring osteoclast actvit
- death to the blasts
- increased RANKL
Thyroid Hormones
- TSH, T4, T3 stiulate osteoblastic activity which causes increased clast activity (hperthyroid= high bone tunrover)
Bone Mass and Aging
men and women: puberty - 20s: peak bone mass and rapid increase
as women age, they lose bone mass
- in 40s-50s menopause: > 7% bone loss per year for > 7 years
as mena ge: they lose less than 1% yearly unless they ahve risk facotrs (chronic steroid use, hypogonadism)
Diagnosis of OP
prevention of OP is key!!
- general recommendation to help decrease risk (smoking, decrease drinking, increase exercise)
- address individual risk factors of pt.
- most who are diagnosed are found from screening routinely or screening because of their risk factors (previous fracture)
- pain is NOT a symptom
for all postmenopasusal women and men > 50
- a BMD measurement for high risk w/o previous fragiity fracture is needed
- if they have had fracutre: can be dx. without the test but still need to get it to see treatment
Guidelines
- T-score of -2.5 or less at spine or hip by DEXA
- hip fracture (with or without DEXA)
- Vertebral, proximal humerus, pelvis or distal forearm fracture + osteopenia of DEXA
- FRAX score: > 3% risk for hip fx in 10 years, > 20% risk of OP fx. in those with osteopenia
Lifestyle Modifications for OP
medications to be cautious with
- stop smoking
- avoid excess alcohol
- adequte dietary intake of calcium and vit D3
- Exercise: weight bearing!! 30 mins 5x week (balance and weight training)
Meds to be Cautious with
- glucocorticoids
- anti-convulsants
- PPIs
- excessive thyroid replacement
others
- calcineurin inhibitors
- GnRH antagnoist (prostate ca)
- aromatase inhibt. (breast cancer)
- cancer chemo
- SSRIs
- antiretrovirals
Primary Prevention of OP
Secondary Prevention of OP
Primary Prevention of OP
- excessive alcohol use
- smoking
- low body weight
(non-mod)
- early menopause
- family history of fx.
Secondary Prvention of OP
- alcoholism
- AK
- CKD
- COPD
- Hyperparathyroidism
- hyperthyroid
- malabsorbtion dx.
- RA
- Dm (1 or 2)
- Vit D deficiency
Assessment
Presentation
Labs
Assessment
- check height trends
H & P
- check hypogonadism
- vit D def.
- malabsorbtion diseases
- MM
- steroid use
- hyperparathyroidism
- organ transplant
Presentation of pt.
- commonly, coming in for low back due to a compression fracture
- most commonly: the T7-8 and T12-L1
Labs
- fasting CMP
- serum phosphours
- vit D (inactive)
- PTH
- TSH
- 24 hours calcium
- CBC
- testosterone
Bone Density Measurement Specifics
FRAX Tool Specific
Vertebral Fracture Assessment
Bone Density Measurement
best predictor of fracture risk = DEXA
- spine (L1-L4) and hip (proximal femur)
- no guidelines for how often and when to stop
- all of those 65+ women with fx risks
- USPFTF: all women > 65, cat. I for men
FRAX: alogrithm to predicton 10 years of fx. risk
- of hip fx. or major osteoporotic fx.
- NO valid in.. those gett OP treatment, < 40 or > 90
- for white, black, latinxa, and asaaain
- only looks at T score at the HIP not the spine
Vertebral Fracture Assessment
- assocaited with future fracture risk and morbidiity (5x greater risk even if they have no symptoms)
- can occur in those with BMD > -2.5
- also consider, women older age, ostepenia, low-trauam fx. height loss of 1.5+ inches, recent steroid use
Treatment
Non-pharm
calcium
vit D
exercsie
Adequate Calcium Intake
- postmenopausal women > 50 & men >70 = 1200mg/day
- men 51-70 and women < 50 = 1000 mg/day
- upper level of intake should not be > 2000
Vit D recommendations
- men and women < 50 = 400-800
- women and men 50+ = 800-1000
- goal = into normal ranges
- upper limit = 4,000
Exercise
- weight beraing recommended
- muscle strengthening and balance
Pharmacological Treatmetn of OP
- Bisphosphonates
- names
- MOA
- Contraindications & cautions
MOA: inhibit resorbtion of bone
Alendronate & Risedronate = weekly
Risedronate & Ibandronate = monthly
- IV zoledronic acid
- IV ibandronate
Contraindications
- crcl < 35
- esopheagela disorder: strictures, achalasia (pill esophagitis)
Caution in
- dental disease (can cause osteonecrosis
- correct hypocalcemia priot to starting
d/c when life expect. < 2 years or no longer mobile
reassess fracture risk 3-5 years after
oral meds
- take first thing AM
- full galss of water
- upright for 30 minutes
- do not eat/drink for 30 minutes
Side Effects
- chalkstick leg fracture
- osteonecrosis of jaw
- abd pain, esophagitis
- MSK pain
- acute phase response: flu like ilnness with zoledronic acid
OP treament
RANKL inhibitor
Denosumab : monoclonoal antibody that inhibits osteoclasts
- alternative to bisphosphonates
- reseerved for those who do not tolerate bisphophsphonates ( crcl < 35)
OP Treatment
Teroparatide
parathyroid horomone like (doesnt make sense…..)
- enhances osteoblast activity and number
- subQ injection
- preferred treatment for those with OP due to chronic steroid use
BLack Box Warning
- pagets disease
- h/o skeletal irradiation (tumor)
OP Treatment
Sclerostin Inhibitor- Romosozumab
monoclonal antibody: works on bone metabolism
- increase blasts
- decrease clasts
- anabolic- not anti-resorptive
Black Box
- increased risk for MI, stroke, CV death
- contraindicated if CV event in past 12 months
Selective Estrogen Receptor Modulators (SERMS)
how they work
Raloxephene
SERMS
- estrogen agonist in the bones (increase estrogen to bone: better change of blast > clast)
- decrease estrogen in breast and uterine tissue (post-meno) good for cancer treatment!!
- used for prevention and treatment of OP in post-menopausal women
Raloxephene
- decreased bone turnover to maintain BMD
- decrease risk of vertebral fractures
- increase risk of VTE and sroke
Side Effect: flushing, hot flashes, leg cramps , edema
OP Treatment
Calcitonin
last line use; not crazy effective
hormonal inhibitor of bone resorbtion
- possibel analgenic effect for compression fx. pain
recommnede no tto use in postmenopausal females for inc. breast cancer risk
OP monitoring
sereial BMD DEXA scan
- every 1-3 years for OP or penia
if loss of BMD on treatment…
- think nonadhearance
- secondary cause
- failling treatment
dont chagne meds from one to the otehr if failing, no efficacy
Management of Osteopenia
t score between -1 and < -2.5
- no medical treatment with meds.
- fix vit D and calcium dosing
- weight bearing exercsie
- stop smoking
- decrease alcohol
- reduce fall risk
- avoid (PPIs and steroids)
Paget’s Disease
Etiology
Patho
Etiology
- localized areas of increased bone remodeling resulting in malignant transformation and changes in bone architecture
- most causes are unknonw, genetic predisposition SQSTM1 gene
- increased risk for deformities and fractures
Patho
- increased osteoclasic bone resorobtion = lytic lesions within the bone
- increased number of osteoblasts = disorganzied osteoid formation
Pagets Disease
Presentation and Symptoms
Presentation
- asymptomatic: found on xray or increased alk phos found on normal labs
- if symptomatic: pain is most common
- pain is localized to the site
- secondary osteoarthritis in hips, knees and vertebrae
- aching, deep and worsening at night
Symptoms
- pain
- osteoarthritis
- bone deformities: bowing legs, leg-length issues, gait issues
others…
- radiculopathy: due to compression of nerves due to inc. bone growth
- chronic back pain
- imapired function
- skull disease (enlarged size)
- headahces
- sensorineural cahnges (cochlear)
- vertigo
- crainl nerve issues
- visual issues
Vertebral Involvement
- spinal stenosis (narrowing of the canal inside the vertebrea due to inc. bone growth)
- kyphosis
- parlysis (rarely)
Pagets Disease
- Labs
- Imagings
Labs
- serum calcium and phosphate will be NORMAL
- increased alkaline phosphatase from bone not liver
- vit D screen (could be low)
- increased urinary hydroxproline
- bone turnover markers can be helpful
Imaging
- localized abnormal areas: mixed llytic and sclerotic lesions
- “bone islands” of encircled sclerotic bone
- “cool wool spots” of bone depost abnormalites
Pagets Disease
Treatment
Asymptomatic : survellience and treat when it becomes worse
Symptomatic : Bisphosphonates
- need to suppress the bone turnover and remodeling process
- IV zoledronic acid is first line!!!
- pre-treat before ortho proceudres (can trigger increase turnover)
IV zoledronic Acid
- first dose effect: flu like symptoms
- fever, fatigue, myaliga
- bone pain
- ocular problems
Pagets Disease
complications
- deformities, gait instability, falls
- pathologic fractures (lytic lesions)
- arthritisi
Malignancy Transformations
- increase boney pain, sudden rise in alk phos. new lesions = be sus of cancer
- immoblie can lead to increase calcium and renal stones
- high output cardiac failure due to increase vasculatiry of bones increase amout of circuatlion
Survellience with alk phos annually
