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

1. Adrenal cortex
• Cushing’s disease
• Addison’s disease
2. Gonadal disorders
• Hypogonadism
3. Pituitary
• Acromegaly
• Hypopituitarism
4. Pancreas
• Diabetes mellitus
5. Thyroid
• Hyperthyroidism
• Hypothyroidism
6. Parathyroid
• Hyperparathyroidism

B. Drugs and substances

1. Corticosteroids
2. Heparin
3. Anticonvulsants
4. Immunosuppressants
5. Alcohol

C. Marrow replacement and expansion

1. Myeloma
2. Leukemia
3. Metastatic disease
4. Gaucher’s disease
5. Anemias (sickle cell, thalasemia)

D. Chronic disease

1. Chronic renal disease
2. Hepatic insufficiency
3. Gl malabsorption
4. Chronic inflammatory polyarthropathies
5. Chronic debility/immobilization

E. Deficiency states

1. Vitamin D
2. Vitamin C (scurvy)
3. Calcium
4. Malnutrition

F. Inborn errors of metabolism

1. Osteogenesis imperfecta
2. 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 3^rd 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

Spinal OP

• 2 kinds of pain:
1. acute - due to #
2. 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

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