Osteoporosis

Quantitative defect of bone characterised by reduced bone mineral density and increased porosity

Aetiology

• Loss of bone mineral density is physiological - starts at ~30 years

• Females tend to lose more bone mineral density after the menopause due to an increase in osteoclastic bone resorption with the loss of protective effects of oestrogen

Type I oseotoporosis

• Exacerbated loss of bone in the post‐menopausal period

• Early menopause may have an influence

• Familial and environmental factors (white Caucasians at particular risk)

• Further risk factors include smoking, alcohol abuse, lack of exercise and poor diet

• Colles fractures and vertebral insufficiency fractures tend to occur in this group

Type II osteoporosis

• Osteoporosis of old age with a greater decline in bone mineral density than expected

• Risk factors are similar with the added risks of chronic disease, inactivity and reduced sunlight exposure (Vitamin D)

• Femoral neck fractures and vertebral fractures predominate in this group

Secondary osteoporosis

• Drugs especially corticosteroid use and aromatase inhibitors (breast cancer)

• Alcohol abuse

• Malnutrition

• GI disorders - hepatic insufficiency, malabsorption, malnutrition, deficiency of vitamin C and D

• Chronic disease - CKD, malignancy, rheumatoid arthritis

• Endocrine disorders - Cushing’s, hyperthyroidism, hyperparathyroidism

• Immobilisation

Localised osteoporotis

• Localised osteoporosis can develop through disuse of particular bones

Pathophysiology

• Peak bone mass occurs in young adulthood
• Determined by hereditary factors (polymorphisms in genes regulating bone metabolism) and environmental factors (physical activity, muscle strength, diet and hormonal stasis

• After peak bone mass has been reached, there will be average bone loss of 0.7% per year (normal part of aging)

• In older age, the proliferative and biosynthetic capacity of osteoblasts is redued and response to growth factors is attenuated
• Also as we age there tends to be reduced physical activity

• The reduced density and increased porosity increases the fragility of bone → increases fracture risk
• Fractures after little or no trauma, vertebral compression fracture

Effect of corticosteroids on bone

• Reduction of osteoblast activity and lifespan

• Suppression of replication of osteoblast precursors

• Reduction in calcium absorption

• Inhibition of gonadal and adrenal steroid production

Common osteoporotic fracture sites

• Neck of femur

• Vertebral body - often not identified at the time of injury as stress can be minimal e.g. coughing
• Result in thoracic kyphosis and loss of height
• Once patient has had one vertebral body fracture they are at increased risk of additional fractures

• Distal radius

• Humeral neck

Investigations

Risk assessment tools

• Use an 10 year osteoporotic fracture risk calculator to assess:
• Anyone over 50 years with risk factors
• Anyone under 50 years with very strong clinical risk factors - early menopause, glucocorticoids

DEXA scanning

• Measure of bone mineral density - predicts fracture risk independently of other risk factors
• For every decrease in 1 SD below the mean, fracture risk doubles

• Anyone with a 10 year risk assessment for any OP fracture of at least 10% should be referred for a DEXA scan, as well as any patient over 50 years with a low trauma fracture

• Osteoporosis is diagnosed when bone density is 2.5 standard deviations below the mean peak value of young adults of the same race and sex

• Severe osteoporosis is defined as bone density is 2.5 standard deviations below the mean peak value of young adults of the same race and sex WITH a fragility fracture

• Osteopenia is an intermediate stage where bone mineral density is between 1 to 2.5 standard deviations below mean peak value

Others

• To ensure treatment is safe, and check there is no additional underlying condition contributing to the decreased bone density

• U+Es, LFTs, FBC, PV, TSH

• Consider:
• Protein electrophoresis/Bence Jones proteins - to rule out multiple myeloma
• Coelic antibodies
• Testosterone
• 25OH vitamin D
• PTH

Management

• No treatments can increase bone mineral density

• Treatments aim to slow any further deterioration and hopefully decrease the risk of subsequent fracture

Lifestyle advice

• Increase calcium intake - postmenopausal women aim 1000 mg calcium per day (700 mg recommended for general population)

• High intensity strength training

• Low-impact weight-bearing exercise

• Avoidance of excess alcohol

• Avoidance of smoking

• Fall prevention

Pharmacological management

• Calcium and/or vitamin D supplements if dietary intake is poor/limited sunlight exposure
• Calcium supplements should not be taken within 2 hours of oral bisphosphonates

• Oral bisphosphonates (alendronic acid, risedronate, etidronate) - reduce osteoclastic resorption, first line for the majority of patients
• Consider treatment with when T score </= -2.5
• If ongoing steroid requirement >/= 7.5mg prednisolone for 3 months or more or if there is a prevalent vertebral fracture, consider treatment with T score < -1.5

• Zoledronic acid - once yearly intravenous bisphosphonate, second line for majority of patients e.g. patients with side effects with oral bisphonates

• Desunomab - monoclonal antibody which reduces osteoclast activity, another second line alternative to oral bisphonates

• Teriparatide - recombinant parathyroid hormone; stimulates bone growth rather than reduces bone loss (anabolic)
• Recommended to reduce risk of vertebral and non-vertebral fractures in postmenopausal women with severe osteoporosis
• Recommended over oral bisphosphate in postmenopausal women with at least 2 moderate or 1 severe low trauma vertebral fracture to prevent vertebral fracture

• Romosozumab - monoclonal antibody that binds to and inhibits sclerostin to increase bone formation and reduce bone resorption
• Recommended for postmenopausal women with severe osteoporosis who have had a fragility fracture and are at imminent risk of further fracture (24 months)

Prevention

• Building up peak bone mineral density by way of exercise, good diet and healthy levels of sunlight exposure before bone density starts to decline may reduce the risk of osteoporosis