Metabolic Bone Disorders Flashcards
Which has a higher turnover rate, trabecular or corticol bone?
trabecular
What are the biochemical markers of bone formation?
- Alk P
- Osteocalcin
- Carboxyterminal propeptide of type I collagen (P1NP)
What are the biochemical markers of bone resorption?
N-telopeptide
Carboxyterminal of type I collagen (CTX-1)
What is osteoporosis?
a skeletal disorder characterized by compromised bone strength predisposing to fracture. Bone strength reflects the integration of bone density and bone quality
How is osteoporosis measured/tested?
Central DEXA currently the gold standard to measure bone mineral density
What is the risk of a fracture with a DEXA of -1, -2, and -3
These numbers represent standard deviations from normal bone density and the risk doubles per each SD away from the mean
so if O SD= 1 risk
- 1= 2x more likely
- 2= 4x
- 3=8x
What DEXA T score is diagnostic of osteoporosis?
-2.5 (from -1 to -2.5= osteopenia) OR
Low-trauma (aka fragility) fracture with a T-score greater (more positive) than -2.5
How much does a single vertebral fracture increase the risk of another? 2 vertebral fractures?
1 vertebral fracture increases risk by 5x (and increases risk of hip fracture by 2x), and 2 increases by 12x
Even at the same T-score, _____ increases the risk of fracture
age
What drugs increase the risk of fracture?
glucocorticoids, TCAs, SSRIs, PPIs, long-acting benzodiazepines, antipsychotics
anticonvulsants, aromatase inhibitors, androgen deprivation therapy (prostate cancer Tx)
Risk factors for fracture?
Age, previous low trauma Fx, low BMI, current cigarette smoking
steroid use, rheumatoid arthritis, high alcohol intake, fam Hx of fracture
Who should be treated with osteoporotic Tx?
- those with T-score less than 2.5 after age 50
- osteopenia with Hx of a fragility fracture
- Use FRAX score to decide to treat those younger than 50 with a T- or Z-score less than 2.5 or older than 50 with a t-score greater than -2.5
How do you interpret FRAX
A 10-yr risk of 3+% for hip fracture or 20+% for major osteoporotic fracture is sufficient to initiate pharamcological treatment
What things in a osteoporotic patient might suggest Cushing’s syndrome being the underlying cause?
chronic steroid use, obesity, accelerated weight gain, buffalo hump
What things in a osteoporotic patient might suggest primary hyperparathyroidism being the underlying cause?
hypercalcemia and an elevated PTH with decreased Phosphate
What things in a osteoporotic patient might suggest acromegaly being the underlying cause?
arthralgias, large hands and feet, obstructive sleep apnea
What things in a osteoporotic patient might suggest secondary hyperparathyroidism being the underlying cause?
kidney stones
What things in a osteoporotic patient might suggest hypogonadism (low testosterone) being the underlying cause?
low libido, erectile dysfunction, loss of muscle mass
What things in a osteoporotic patient might suggest hyperthyroidism being the underlying cause?
suppressed TSH, tachycardia, diarrhea, etc.
How is idiopathic osteoporosis treated?
1) optimize lifestyle (stop alcohol and tobacco, increase physical activity, maintain calcium and vitD(30+ng/mL))
2) Pharm intervention (bisphosphonates, etc.)
What is osteomalacia/rickets?
failure to mineralize bone leading to softening of bone most commonly due to vitD deficiency (nutritional, no sunlight, liver disease)
What is Type I VitD Dependent Rickets?
AR disease caused by a defect in 1a-hydroxylase
What is Type II VitD Dependent Rickets?
AR disease caused by defect in receptor response to activated vitD
What is Paget disease of bone?
localized area of lytic then sclerotic bone formation that leads to formaiton of large amounts of poor quality bone that can manifest as enlarged skull, bony pains, and extremity deformities
Complications: hearing loss, bone tumors (osteosarcoma), fractures
Tx of Paget’s disease?
single IV dose (because they have a very long half-life) of bisphosphonates is typically curative
Labs for Paget’s disease?
isolated ALP
What is osteopetrosis?
Too much brittle bone is made (labs are normal and DEXA will be VERY positive) but breaks like chalk
What is osteitis fibrosa cystica?
disease caused by hyperparathyroidism that is primarily seen in primary hyperpTH and ESRD patients with very high PTH levels.
How does OFC present in labs?
elevated PTH, elevated calcium in primary HPT and normal/low-normal calcium in ESRD patients. Elevated ALP
What is the most sensitive and specific radiologic finding of OFC?
subperiosteal resorption of cortical bone, best seen in high-resolution films of the phalanges. A similar process in the skull leads to a salt-and-pepper appearance
Bone cysts or brown tumors may present as osteolytic lesions
How does OFC present histologically?
increase in osteoclasts, marrow fibrosis, and cystic lesions that may contain fibrous tissue (brown tumors)
do a DEXA on the forearm, mostly cortical bone
How does OFC present clinically?
bone pain and sometime spathologic fractures. This osteoporosis is due to preferential loss of CORTICAL bone (osteoporosis is a loss of trabecular bone)
What is fibrous dysplasia?
Replacement of bone with fibrous connective tissue and poorly formed trabecular bone due to activating mutations in GNAS 1.
What are the types of fibrous dysplasia?
It can be monostotic (single bone) or polyostotic (multiple bones)
Association of the polyostotic form with café au lait spots and hyperfunction of an endocrine system such as pseudoprecocious puberty of ovarian origin is known as McCune-Albright syndrome (MAS).
What is the most common form of fibrous dysplasia?
The monostotic form is the most common and is usually diagnosed in patients between 20 and 30 years of age without associated skin lesions.
Describe the polyostotic form of fibrous dysplasia
typically manifests in children under 10 years old and may progress with age.
In polyostotic fibrous dysplasia, the lesions most commonly involve the maxilla and other craniofacial bones, ribs, and metaphyseal or diaphyseal portions of the proximal femur or tibia.
What are the symptoms of fibrous dysplasia?
Expanding bone lesions may cause pain, deformity, fractures, and nerve entrapment.
Labs for fibrous dysplasia?
Hypophosphatemia (may be due to production of FGF-23 by the abnormal fibrous tissue). Ca, PTH, vitamin D – are all normal. Markers of bone turnover can be elevated (ALP)
Radiographic findings of fibrous dysplasia
In long bones, the fibrous dysplastic lesions are typically well-defined, radiolucent areas with thin cortices and a ground-glass appearance. Lesions may be lobulated with trabeculated areas of radiolucency
How is fibrous dysplasia treated?
- Asymptomatic patients may be observed every six months with serial radiographs.
- Symptomatic patients (pain and deformity) may benefit from curettage, bone grafting, and stabilization.
- Bisphosphonate therapy may improve symptoms .
What is the prognosis of fibrous dysplasia?
– The deformity may progress with skeletal growth
-Usually static after growth ceases at puberty (may be reactivated with pregnancy)
