What is osteoporosis? | Reduction of bone mass/ density leading to increase in risk of fracture.
WHO defined it as BMD<-2.5 SD (bone density) and >-1 (osteopenia) but not reliable since 1/3 of females get vertebral fractures and are missed
A better definition is Skeletal disorder characterized by compromised bone strength predisposing increased risk of fracture |
How is the pathophysiology of osteoporosis? | Bone is remodeled by osteoclasts and osteoblasts (equilibrium), till puberty osteoblast activity predominates and at puberty there is more bone formation by sex hormones then just after puberty both blast and clast are equal
After 30 years of age clast predominates decreasing bone mass, in addition females at menopause decrease estrogen and thus decrease bone formation leading to more osteoporosis as estrogen def decreases osteoblast activity and increase osteoclast activity, in addition to indirect effect by causing secondary hyperparathyroidism in collab with decreased Ca2+ intake) |
How are osteoporotic fractures? | Could affect any bone (hip, radius, ulna, vertebra)
If they affect vertebra, they will lose width and people will become shorter in body area |
What are the risk factors of osteoporotic fractures? | Non-modifiable (hx of fracture, female, advanced age, caucasian, dementia)
Modifiable (cigarette smoking, low body weight, estrogen def, low calcium intake, alcoholism, impaired eye sight, recurrent falls, inadequate physical activity, poor health |
What are the possible complications of osteoporosis? | Pain, height loss, kyphosis, activity limitation, restrictive lung disease, altered abdomen, psychological symptoms, cost (in USA and europe =27billion $/year
w |
How is the epidemiology of osteoporosis and fractures? | Osteoporosis prevelance has increased due to increased awareness of the disease, improved tools (BMD), and increased lifespan of individuals
Worldwide: 200 million women suffer from it, US 8 million females and 2 million males, 18 million have low BD (osteopenia), EU we have fractures every 30 seconds, and USA every 20 seconds (1.5 million per year, mostly vertebral and other bones are equally fractured)
Occurs more than heart attacks, strokes or breast cancer |
How are osteoporotic fractures related to increased morbidity and mortality? | 20% death within 1 year
30% become permanent disabled
40% unable to walk independently
80% unable to carry out at least 1 daily task.
Nb of hip fractures worldwide has increased 6 folds
Risk of new fracture after vertebral fracture is 20% for post menopausal women having vertebral fracture) and 26% having other fractures |
How is calcium intake related to osteoporosis? | Inadequate intake --> decreased BM and increased risk of osteoporosis.
Can induce secondary hyperPTH, and adequate intake should be taken prepuberty
Ca daily should be >400mg, RDA should be 1000-1200 mg/day |
How does vitamin D affect osteoporosis? | Vitamin D deficiency causes compensatory hyperPTH -->increases risk of osteoporosis.
It is important for calcium absorption, usually caused by D3 deficiency (from endogenous source skin getting UV light- we get it from fish liver oils, butter, cream, yolk, cheese...)
PTH in kidney causes 1-hydroxylation of D3 cholecalciferol. |
How is vitamin D production? | . |
What is mechanism of action of vitamin D3? | Increased gut absorption, renal reabsorption and bone resorption in case of Ca2+ deficiency
Vitamin D levels seen by serum 25-cholecalceferol level
Most region with vitamin D deficiency is middleast (81%) in postmenopausal women
73% of lebanese population are vitamin D deficient |
Why do we have a prevalent vitamin D defeciency? | Lack of sunlight exposure, scarce in diet, ability decreases with age of skin to produce it, lack of compliance taking supplements, genetics |
What are the effects of inadequate vitamin D levels? | Decreased calcium absorption
Increased PTH
Increased bone resorption
Decreased BMD
Decreased neuromuscular function
Increased the risk of falls
Increased risk of fracture |
What is the effect of estrogen on osteoporosis? | Estrogen inhibit clast and stimulate blasts, deficiency leads to osteoblast forming inflammatory cytokines, inhibit death of clasts and increase their activity |
What is the effect of physical activity on osteoporosis? | Inactivity leads to bone loss, more marked during growth and puberty, not very large effect on adults (cannot restore it from physical activity
In rural countries we have a higher risk of fracture |
What is the effect of chronic diseases on osteoporosis? | May be genetic or acquired disease, due to nutrition, decreased physical activity or remodeling affected, associated disease are hypogonadal, endocrine disorders, nutritional and GI disorders, rheumatic, malignancy, bone disorders |
What are the effects of some medications on osteoporosis? | Steroids increase its risk, thyroxine as well, some Abx, GnRH, heparin... |
What is the effect of cigarette smoking on osteoporosis? | Toxic effect on osteoblasts, modify estrogen metabolism indirectly and secondary effects (respiratory, exercise, nutrition, medications...) |
What are the ways of measuring BMD (bone mineral density)? | Dual energy X-ray absorptiometry ( DXA )
Single energy X-ray absorptiometry (SXA)
Computed Tomography ( C.T. )
Ultrasound |
What is BMD? | Densitometry X ray seeing mineral component of bones.
normal above -1, osteopenia betw -1 and -2.5 and below -2.5 is osteoporotic
We use it with postmenopausal women with risk factors of osteoporosis, females>65 yrs, and patient followup after Rx |
When do we start osteoporotic treatment? | BMD <-2.5 or -2 with risk factors (FRAX score -WHO) |
How is the approach to pt osteoporosis? | Hx, labs (CBC, Ca, PTH, Vit D, TSH), Xray (DXA), biomarkers |
What is the treatment for osteoporosis? | Management of fracture, underlying disease, nutrition, exercise and meds (estrogen- combined with progestins, benifit declines after stopping, progestins increase risk of breast cancer, SERM (selective E response modulators Raloxifene and Tamoxifene prevent cancer and porosis, bisphosphate (postmenopausal prevention, Alendronate 5mg/day and Risedronate 10mg)
Calcitonin (reduce vertebral fractures, analgesic), PTH (but limited use), Fluoride (potent stimulator of osteoprogenitor cells), GH, Statin... |
What is the monitoring done after Rx of osteoporosis? | BMD (repeated once every 2 years)
biomarkers (repeated after 4 months of tx 30-40% changes) |
What is the tx of steroid induced Osteoporosis? | Bisphosphonates |
What is osteomalacia (ricketts)? | Disorders in which mineralization of the
organic matrix of the skeleton is defective
Rickets the growing skeleton is involved
Osteomalacia the adult skeleton is involved, in which the epiphyseal growth plates are closed |
How do we dx rickets? | Radiological features
Lab findings:
- Calcium
- Phosphorus
- Vitamin D |
What is the Rx of rickets? | Vitamin D:
800 IU/day, prevent vitamin D defeciency.
Active form if needed: 1,25 (OH)2D3 (Calcitriol) 0.25-0.5 ug/d
Pharmalogical doses may be needed (50,000 IU/week for 3-12 weeks) followed by maintenance therapy 800 IU/d
In malabsorption: Vitamin D IM
Calcium:
1.5 - 2 g/d, PO |