Osteoporosis
Definition
- decrease in bone mass to a level where #’s occur
- normal bone composition
- osteopenia = decreased bone mass in the absence of spontaneous #’s
- osteoporosis = clinical # syndrome
- osteomalacia = decreased mineralization, can co-exist with above
Osteopenia
- nonspecific term indicating reduction in bone mass
- determined by radiographic study
4 groups
- osteoporosis
- osteomalacia – abN mineralization
- osteitis fibrosa
- malignant dx.
Classification
Primary
Idiopathic juvenile osteoporosis
Idiopathic osteoporosis in young adults
Involutional osteoporosis
- type I (“postmenopausal” osteoporosis)
- type II (“senile” osteoporosis)
- type III (osteoporosis associated with increased parathyroid function)
Secondary (partial listing)
A. Endocrine
- Adrenal cortex
- Cushing’s disease
- Addison’s disease
- Gonadal disorders
- Hypogonadism
- Pituitary
- Acromegaly
- Hypopituitarism
- Pancreas
- Diabetes mellitus
- Thyroid
- Hyperthyroidism
- Hypothyroidism
- Parathyroid
- Hyperparathyroidism
B. Drugs and substances
- Corticosteroids
- Heparin
- Anticonvulsants
- Immunosuppressants
- Alcohol
C. Marrow replacement and expansion
- Myeloma
- Leukemia
- Metastatic disease
- Gaucher’s disease
- Anemias (sickle cell, thalasemia)
D. Chronic disease
- Chronic renal disease
- Hepatic insufficiency
- Gl malabsorption
- Chronic inflammatory polyarthropathies
- Chronic debility/immobilization
E. Deficiency states
- Vitamin D
- Vitamin C (scurvy)
- Calcium
- Malnutrition
F. Inborn errors of metabolism
- Osteogenesis imperfecta
- Homocystinuria
Juvenile Osteoporosis
- generalised OP in otherwise normal pre-pubertal children (9-14 yrs)
- unknown aetiology
- Se values (Ca, Ph, ALP, parathyroid hormone) normal
- slight << in 1,25 dihydroxy vitamin D
Clinical
- low back & lower extremity pain
- kyphotic deformity
- slightly more common in boys
mild
- back pain & vertebral #s
moderate
- back & lower extremity pain with #s
- return to normal function
severe
- pain & fractures
- no return to N activity after puberty
X-Rays
- osteopenia with metaphyseal #s
- wedging & collapse of vertebral bodies
- “codfish” appearance
- biconcave vertebrae
Treatment
- exclude other causes of OP (Diff. dg)
- metabolic bone dx.
- leukemia
- Cushing sy.
- osteogenesis imperfecta
- self limiting
- naturally improves with onset of puberty
- kyphosis also better
- modification of activities, Ca & vit. D supplements
- bracing for kyphosis
- surgery
- poor results – poor bone stock
Primary adult (involutional) osteoporosis
- commonest bone disease
- no endocrinopathy or other dx.
- high rate of morbidity & mortality
Incidence
- 20 million in USA
- >> incidence d/t > longevity
- mostly elderly white females ( > 50-55 yrs)
- 1/3 of females > 65 - at least 1 vertebral #
- 1/4 of females > 80 - hip #
- men rarely - andro-pause about 15 yrs later
- rarely occurs in blacks
Riggs & Melton classification of primary OP
type 1 - Osteoclast mediated
- rapid bone loss in recently menopausal women
- female : male 6 : 1
- mainly involves trabecular bone - distal radius & vertebrae
type 2 - Osteoblast mediated
- female : male 2 : 1
- related to ageing, Ca loss, lack of activity & decreased bone formation
Bone Metabolism
- peak bone mass in the middle of the 3rd decade
- the greater the peak bone mass, the better the chance of avoiding OP in later life
- after peak 40 yrs bone loss occurs at
- 0.3% / year in males
- 0.5% / year in females
- loss of 2 to 3% per year at the onset of menopause occurs
- all adults loose bone but only 20 to 30% of females & 10 to 20% of males > 65 years develop OP
Bone Remodelling / Loss
- constant resorption & formation of bone thro’ out life
- cycle of ~ 4-6 months
Bone formation - osteoblasts
- cells of marrow stromal origin
- organic matrix type 1 collagen which undergoes mineralization
Bone resorption - osteoclasts
- multinucleated cells arising from macrophage precursors
- cause resorption by
- isolating a segment of bone forming a Howship lacuna
- enzymatic degradation by carbonic anhydrase & acid proteases
- imbalance that enhances resorption or impairs formation -> net bone loss
- may be rapid or slow
- may or may not be reversible
- young adults -> bone formation = erosion -> no net bone loss
- with age -> less bone formed with each remodelling cycle
- trabecular plate perforation -> new bone only laid on edges of perforation = slow & irreversible loss
- causes of rapid bone loss (new remodelling cycles):
- menopause
- immobilization
- anorexia
- hyperparathyroidism
- hyperthyroidism
- high dose steroids
- rate of trabecular bone loss > cortical loss (greater surface area)
- spinal #’s are 1st manifestation
Pathogenesis (causes) of bone loss
1. Age related factors
estrogen deprivation
- menopause, oophorectomy
- >>number of resorption sites -> therefore >> bone loss
- oral contraceptives protect against loss
inactivity
Ca & vit D deficiency
- exact role of Ca deprivation is not known
- lifelong high Ca intake -> << hip & wrist # rate
- vit D - essential for Ca absorption from GIT
- << vit D leads to << Ca which leads to >> PTH secretion & therefore erosion
- with increasing age 1,25 dihydroxy vit D may decrease because of:
- less sun exposure
- declining renal function
- GIT resistance to 1,25 dihydroxy vit D
- need >> amounts of Ca & vit D with increasing age
Calcitonin deprivation
- has an anti-erosive effect on bone
- decreased levels at menopause leads to > bone erosion
2. Genetic factors
- low bone mass in 1 or both parents
- White or Asian
3. Medical factors
oophorectomy
hysterectomy
- results in decreased ovary blood flow -> less hormone production
steroids (> 7.5 mg\day)
- << Ca absorption from GIT - 2° HPT
- << liver metabolism of vit D - 2° HPT
- affect osteoblast activity
hyperparaTh
hyperthyroidism
anticonvulsants
- Ca malabsorption & vit D catabolism - 2° HPT
gastrectomy
small bowel resection
- malabsorption
myeloma & mets
4. Lifestyle factors
alcohol abuse
- decreased bone formation & increased erosion
- metabolic effects which cause bone loss eg. < GIT absorption, < liver function
low weight or anorexia
inactivity or excessive exercise
smoking
- associated with < gonadal hormone levels
high protein diet
- equals hi phosphate intake
- phosphates bind Ca in GIT & < absorption & increase Ca urine excretion
Mnemonic - DENNIM
Clinical
- not a pain syndrome
- presents mostly with #s
- OP in obese women or men = atypical & always exclude 2° causes
Lab
- blood tests N
- full screening if < 45 yrs old or suspicion of 2°
- FBC, diff.count
- ESR
- Ca, Ph
- PTH & thyroid hormone levels
- increased bone turnover
- bone formation markers - ALP
- bone erosion markers - urine hydroxyproline
- serum creatinine
- serum protein electrophoresis
- gonadal & gonadotrophic hormone concentrations
- in women < 50 yrs & in all men with OP
Diff. dg (most common)
- 1° HPT, hyperthroidism, steroids, osteomalacia, myeloma, mets
Types of involutional osteoporosis
Type 1(Postmenopausal) | Type 2(Senile) | |
---|---|---|
Age | 50 to 70 | > 70 |
F:M Ratio | 6 : 1 | 2 : 1 |
Bone loss | Trabecular | Cortical |
Rate of loss | Rapid | Not Rapid |
# sites | Vertebrae | Vertebrae |
Distal Radius | Hip |
Spinal OP
2 kinds of pain:
- acute - due to #
- mild intermittent - d/t resultant deformity
vertebral body wedge compression #s:
- occur spontaneously
- in lower dorsal or upper lumbar spine
- back pain for about 6 weeks
- resolves with bed rest & analgesia (compare malignant disease)
- vertebral deformity, kyphosis & loss of height is permanent
- no neurology (compare pain in disc disease)
- no canal stenosis & no cord compression
- biconcave vertebral bodies from compression #’s
Features suggestive of malignancy:
- severe pain not relieved by rest or analgesics
- pain persists for > 6 weeks
- isolated # vertebra in upper dorsal spine
- sciatica
- cord compression
- shaft # of long bone
# of NOF
- usually from a fall from standing height
- sometimes # occurs before the fall
Other #’s of osteoporosis
- distal radius
- proximal humerus & ribs
X-rays
- << density
- thin cortex in long bones
- wedging or bi-concave vertebrae
Assessment of Osteoporosis X-rays/h2>
Bone density
- based on varying shades of grey of the image
- inaccurate because of variations in radiographic technique
- approximate assessment of amount of bone present
Vertebral compression fracture
- most obvious structural alteration
- described as vertebral crush, wedge or concavity (= fish tail) #
- biconcavity also occurs in sickle cell dx. & Gaucher’s dx
- most commonly in the low dorsal & upper lumbar regions
Singh index
- denotes the structural loss of groups of trabeculae in the proximal femur
- graded from VII (N) to I (severe bone loss)
- Singh index IV & below associated with vertebral #
- X-ray taken with hips in 15° IR(big toes touching) to prevent super imposition of GT
- cannot be used if the trabecular pattern distorted by arthritis or previous surgery
Vertebral trabecular pattern index (VTPI)
- reflects progressive trabecular bone loss similar to Singh index
- earliest sign of OP -> accentuation of vertical vertebral trabeculae which results from disappearance of horizontal trabeculae
- trabeculae become thinner & more widely spaced
- eventually they become so thin and few that they become invisible and the vertebra resembles an empty box
- with VTPI 1 and 2 vertebrae fracture spontaneously
Metacarpal cortical index (MCI)
- measures cortical bone density
- both hands are X-rayed, using single emulsion film for fine details
- outer width D & medullary width d measured at mid-length of 2nd metacarpals
- cylindrical shape
- non-dominant hand reflects general skeletal mass
Bone mineral densitometry
Dual energy X-ray absorptiometry (DEXA)
- currently “gold standard” of bone mineral densitometry
- in patients with high BMD a large proportion of the X-ray energy absorbed by bone & less of it recorded by the detector than in patients with low BMD
- recorded data compared with age & sex-matched control values with the aid of a computer
- areas examined by DEXA
- lumbar spine, proximal femur & total body
- falsely high spine values may be in patients with osteophytes & aortic calcification or fractured vertebrae
- BMD = measured bone mineral content/measured bone area
- radiation dose low
Treatment
- protective oestrogen therapy
- oestrogen 0,625 mg daily (Premarin°)
- calcium supplements
- 1,5 - 2 g daily (Titralac°)
- vitamin D supplements
- calciferol 50 000 U weekly
- biphosphonates
- inhibit osteoclasts --> anti-erosive
- Fosamax°, Didronel°
- fluoride therapy
- not for cortical OP
- calcitonin
- anti-erosive
- in acute spinal # phase
- anabolic steroids
- side effects
Conclusions
- prevention is the best solution
- maximise peak bone mass & reduce post-menopausal & age associated bone loss
- adequate Ca intake during growth
- Ca + vit D supplementation post-menopausally
- life time habit of exercise
- elimination of falls
- estrogen is the drug of choice for the prevention of post-menopausal bone loss
- calcitonin is the drug of choice for those who can’t take estrogen or have pain due to #
- bis-phosphonates (alendronate) has good anti-erosive properties with minimal side effects
- fluoride may have a beneficial role