Metabolic bone disease Flashcards
define osteoporosis
syndrome associated with low bone mineral density and microarchitectural deterioration of bone tissue leading to an increased risk of fractures
asymptomatic until fractures occur
risk of fractures rise as bone density falls
basic pathophys of osteoporosis 2
imbalance between bone formation and bone resorption
increased activity of both osteoclasts and osteoblasts leads to bone loss and osteoclast resoprtion takes weeks and osteoblast bone formation takes months
microscopically
-loss of trabecular bone (both mineralised and collagen components)
risk factors for osteoporosis reducing bone density 9
deficiency of oestrogen in females
deficiencey of androgens in males
sharp drop in bone density in early menopause (multifactorial)
endocrine
-DM
-hyperthyroidism
-hyperparathyroidism
GI conditions
-crohns
-UC
-coeliac diseae
-chronic pancreatitis
CKD
Chronic liver disease
COPD
immobility
BMI <18.5
risk factors for osteoprosis independent of bone denisty 7
age-
oral corticosteroids
smoking
alcohol
previous fragility fracture
rheumatolgy conditions: RA, other arthropathies
parental history of hip fracture
risk factors for osteoporosis mechanism unclear 6
SSRIS
PPIs
anticonvulsants- carbamazepine
aromatase inhibor
GnRH antagonists
TZDs
define bone mineral denisty
measure of amount of bone mineralisation
measured with DEXA scan
define DEXA scan
compares observed BMD with that of normal young adult (T-score)
and that of aged-matched controls (Z score)
measured at lumbar spine (L1+4) + Femoral neck
how is osteoporosis defined by DEXA scnan
T score <-2.5
> -1=normal
<-1 but >-2.5 represents osteopaenia
> -2.5 & fracture= osteoporosis
describe common fragility fractures
occurs with low energy mechanisms that would not normally be expected to result in a fracture
most commonly simple fall:
-hip fractures
-vertebral (crush) fractures
-distal radius fractures
-humeral neck fractures
tools to determine fracture risk 3
FRAX
-fracture risk assessment tool
Qfracture
DEXA
who should undergo assessment of fragility fracture risk
all women age 65y and older
men age 75 and older
regardless of clinical risk factors
all women 50-64 and men 50-74 with:
-previous osteoporosis fragility fractures
-use of oral steroids
-Hx of falls
-low BMI
-smoker
-high alcohol intake
people under 50 with:
-current or frequent oral steroid use
-untreated premature menopause
-previous fragility fracture
considerations for treatment of osteoporosis
exclude non-osteoporotic causes for fragility fractures:
-metastatic disease
-Myeloma
-osteomalcia
-Pagets
exclude vit D deficiency and inadequate calcium intake
treatment for osteoporosis 8
excersise- weight bearing activity
reduce fizzy drinks - esp colas
HRT for menopause <40yo
vit D ± calcium (if calcium intake inadequate)
bisphosphonates
raloxifene
calcitonin
denosumab
MOA of bisphosphonates
reduce bone resporption and bone tunrover
*-issues with compliance
MOA of raloxifine
selective oestrogen receptor modulation (SERM)
agonist on bone and cholesterol
antagonist on mammary/uterine tissue
MOA of calcitonin
thyroid hormone
binds to osteoclasts and inhbits bone resoprtion
salmon calcitonin has much higher affinity for human calcitonin receptors than human calcitonin
has some antigenic side effects
MOA of denosumab
monoclonal antibody to RANKL
inhibits osteoclast formation
MOA of teriparatide
recombinat PTH
anabolic effect
-actiavtes osteoblasts more than osteoclasts
define osteomalaica and rickets and the difference between them
a qualitative bone disorder due to defective mineralisation of osteoids
may happen before skeletal maturity-> rickets
or after skeletal maturity-> osteomalacia
BOTH USUALLY DUE TO VIT D DEFICIENCY
-VIT D INDEPENDENT FORMS ALSO
basic pathophys of rickets (osteomalacia)
poor calcification of cartilage matrix of growing long bones
occurs at zone of provisional calcification
-fraying and widening of metaphysis called cupping
leads to increased physeal width and cortical thinning and bowing
Vit D dependent forms of rickets (osteomalacia) 4
-and causes (0,2,4)
low exposure to UV radiation
low oral intake
-low dietary intake
-breast milkd has low amounts of vit D
low intestinal absorption
-CF
-chronic pancreatiis
-coeliac disease
-gastrectomy
underlying problems
-defective Vit D metabolism
drugs
-cytochrome P450 inducers
-anticonvulsatns (pheytoin, carbamazepine, phenobarbitone)
hepatbobilary disea
renal disease
alcoholism
tumours
Vit-D independent forms of rickets (osteomalacia)
partial defects in renal tubular functioning (renal tubular acidosis, fanconi syndrome)
drugs
-bisphosphonates
-fluoride
-excessive use of phosphate binding antacits
clinical features of rickets 6
aching bones and joints
lower limb abnormalities:
-in toddlers genu varum (bow legs)
-in older children - genu valgum (knock knees)
‘rickety rosary’ - swelling at the costochondral junction
kyphoscoliosis
craniotabes - soft skull bones in early life
Harrison’s sulcus
treatment for rickets (osteomalacia) 5
replace missing components
-vit D
-calcium ± vit D
-calcitriol (syntehtic D3)
-phosphate
surgical correction in selected cases
osteomalacia clinical features 4
bone pain
bone/muscle tenderness
fractures: especially femoral neck
proximal myopathy: may lead to a waddling gait
define pagets disease
-what cuases it
disorder of bone remodelling
starts with increased osteoclast activity
can be monostotic or polyostotic
-likely viral aetiology
-paramyxovirus + genetic susceptibility
3 phases of pagets disease
lytic- active
mixed- active
sclerotic (inactive)
*-all three phases may coexist in the same bone
comon sites of pagets disease
femur
tibia
pelvis
skull
spine
biochem findings in pagets disease 3
calcium and phosphate normal
alkaline phosphate raised
urinary hydroxyproline raised
clinical features of pagets disease 6
localised pain and tenderness
increased focal temperature due to hyperaemia (due to hypervascularity)
increased bone size
bowing deformites
kyphosis of spine
decreased ROM
(75% asymptomatic at time of diagnosis)
complications of pagets disease 8
increassed deformity and pathological fractures risk
increased risk of OA
hearing loss
-sensorineural hearing loss
-conductive hearing loss
neural compression
malignant transformation - eg osteosarcoma (1% of cases)
high output congestive cardiac failure
hyperparathyroidism
intramedullary haematopoesis
radiological features of pagets disease in the skull 4
osteoprososi circumscripta
cotton wool appearance
diploic widening
tam o’shanter sign
radiological features of pagets disease in the pelvis 3
coritcal thickening and sclerosis of iliopectineal and ischiopubic lines
acetabular protrusion
enlargement of pubic rami and ischium
radiological features of pagets disease in the long bones
blade of grass or candle flame sign
lateral curvature of femur
anterior curvature of tibia
radiological features of pagets disease in the spine
picture frame sign
squaring
vertical trabecular thickening
treatment of pagets diseas 3
expectant if syx minimal
bispphosphonates first line
cacitonin
what needs to be watched when treating pagets disease 2
excessive bleeding during arthroplasty/fracture fixation
issues with limb alignment with significant deformiteis in knee arthroplasty
other conditions affecting bone mineralisation
Hypoparathyroidism
Hyper/hypocalcaemia
Hyper/hypophosphataemia
Hypercalciuria
Renal osteodystrophy
Osteogenesis imperfecta
Osteopetrosis
Hypophosphatasia
Fibrous dysplasia
