Metabolic bone disease encompasses three conditions characterized by disordered bone turnover, with an imbalance between bone formation and resorption, resulting in an increased risk of fracture.
- Paget’s disease of the bone
- The most common metabolic bone disease
- There is reduced bone density- there is normal mineralization of bone, but not enough of it!
- Affects 30% of over 50s, women four times more affected than men (reasons below!)
- 40% of women over 50 will have an osteoporotic fracture in their lifetime
- Age: Maximum bone density is reached in the third decade, after which there is a 0.3-0.5% loss per year (which may reach as high as 30-40% in established osteoporosis!). Therefore, the most important primary RF is age
- Estrogen deficiency: post menopausal bone loss is markedly increased, thought to be due to the fact that there is increased osteoclastic avtivity in estrogen deficient states. Early menopause will therefore increase osteoporosis risk
- Family history
- Drugs: steroids!
- Systemic disease: Cushing’s disease (as with steroid usage, the body is exposed to high circulating levels of glucocorticoids), or thyrotoxicosis
- Malabsorption: IBD or coeliac disease
- Poor diet
- Excess alcohol
- Sedentary lifestyle
- Amenorrhea (for example due to extreme weight loss in athletes)
- Osteoporosis is itself asymptomatic, but it increases the likelihood of pathological fractures occurring (more information on pathological fractures can be found here)
- Characateristic sites for osteoporotic fractures include:
- Wrist (e.g. Colles’ fracture)
- Neck of femur
- Crush/ wedge fractures of vertebrae (may present subtly with a gradual reduction in height). NB beware the lumbar fractures which are metastatic, not osteoporotic. Commonest cancers to metastasise to bone are breast, prostate, lung, kidney and thyroid. Therefore examine the prostate in men, and the breast in women, if a malignancy is suspected to rule out these common cancers which occur at a similar time to osteoporosis!
- Neck of humerus
Compression/ wedge fractures seen in L1 and L3 vertebral bodies
Fractured neck of femur. It is intracapsular and therefore at risk of avascular necrosis, likely to require a hemiarthroplasty procedure.
- XR has a low sensitivity and specificity for osteoporosis
- Diagnosis is rather made by a DEXA scan which assesses bone mineral density (BMD, g/cm3)
- A DEXA machine will generate a T- and Z-score.
- The T-score compares the BMD to that of a young, healthy adult, while the Z-score matches BMD to age and sex matched control patients
- A T-score over 2.5 standard deviations (SDs) away from the mean (written as -2.5, as the value will be lower!) diagnoses osteoporosis
- A T-score 1-2.5 SDs away from the mean is osteopenia, an important osteoporosis precursor, where lifestyle factors and diet supplementation are recommended to prevent/ delay progresson to full osteoporosis.
- Bloods for ALP, Calcium and Phosphate show no abnormalities
- Treat any underlying conditions (e.g. hyperthyroidism) and review medications
- Lifestyle factors- stop smoking, reduce alcohol, lose weight and exercise
- Bisphosphonates are first line. They reduce bone resoprtion and increase bone formation.
- E.g. alendronic acid, 70mg once per week (has largely superceded the 10mg daily regimen due to inconvenient regimen- see below)
- Must be taken first thing in the morning, 20-30 minutes before breakfast or other drugs, with a glass of water, and patient must then remain sitting or standing upright for 30minutes to avoid side effects below
- Side effects include abdominal pain, nausea, photosensitivity, oesophageal ulceration.
- If not tolerated, a yearly infusion of Zolendronic acid is available
- Strontium renolate. Strontium is in the same periodic group as calcium and is effective in reducing fractures
- Selective Estrogen Receptor Modulators (SERMs) such as Raloxafene are effective as agonists at the estrogen receptor in bone, while they do not promote cause endometrial cancer, due to their selective agonist action.
- PTH derivatives, effective at reducing fractures, are recommended by NICE only when bisphosphonates are not tolerated.
- HRT is no longer recommended as treatment due to the breast cancer risk.
In osteomalacia there is defective bone mineralization. So there is normal bone quantity, but decreased quality.
Known as rickets in childhood when occurring during bone growth (i.e. before epiphyseal fusion).
- Of calcium, phosphate or vitamin D.
- Calcium and phosphate deficiencies are very rare.
- Vitamin D (synthesized in the skin in response to sunlight, or taken up in the diet- oily fish, milk, eggs, fortified breakfast cereal) is converted to it’s active form (calcitriol) by hydroxylation first in the liver, then the kidney.
- Calcitriol promotes calcium absorption from the intestine and regulates appropriate bone growth and remodeling by increasing osteoclast number.
- Risk factors for vitamin D deficiency include reduced sunlight exposure, poor diet, or any cause of malabsoprtion, especially Coeliac’s and Crohn’s disease.
- Renal osteomalacia occurs when renal failure means the kidneys can longer convert vitamin to calcitriol by hydroxylation
- Hydroxylation of vitamin D in the liver precedes the kidneys in the activation of vitamin D to calcitriol. Liver disease will thus decrease circulating calcitriol precursors.
- Further, cirrhosis may cause malabsoprtion
- Drugs, such as anti-convulsants, which induce liver enzymes will also cause an effective vitamin D deficiency
- There may be vitamin D resistance – treatment here is via high doses of vitamin D
- Often presents insiduosly with diffuse bony pain
- Phosphate depletion within muscles may cause a proximal myopathy resulting in a waddling gait.
- In children, rickets may present with knock-knees (valgus deformity) or bow legs (varus deformity), and mild symptoms of hypocalcaemia
- There may be easy fatiguability
The varus "bow-legged" appearance of a child with rickets
- XR may show Looser’s zones- incomplete stress fractures often found on the neck of femur, neck of humerus, scapula or pubic rami.
- May be loss of cortical bone
- In rickets there are cupped, ragged metaphyseal surfaces
- Definitive diagnosis is via bone biopsy of the iliac crest which shows decreased mineralization
- ALP is raised
- Serum calcium is normal or slightly low, as it is maintained by PTH at the expense of bone (PTH will therefore be high)
Looser's zone seen in the femur
- Depends on underlying cause but may include:
- Increased sunlight exposure
- Vitamin D and calcium supplementation
- Treatment of underlying disorders
This is a disorder of bone remodeling- increased osteoblast and osteoclast activity causes bone enlargement, deformity and weakness.
- Onset usually late middle age (rare in uder 40s)
- M = F
- Rare in Asians and Africans
- 3-4% of over 55 year olds, 10% in over 80s
- May be asymptomatic
- May have mild pain and warmth over site of remodeling
- Common sites of bone enlargement include the skull (hats no longer fit!), femur, clavicle, and tibia, which can become bowed (a.k.a. “sabre tibia”)
- Deafness due to compression of CNVIII by enlarging skull bones
- High output heart failure (bones are highly vascular)
- Sarcoma- occurs in 1% of those affected >10yrs
- XR changes: sclerotic (hyperdense) bone, tickened cortex, course trabeculae
- Radionucleotide scans may show areas of increased density
- Highly elevated ALP
- Calcium and phosphate normal
- Largely supportive, with analgesia if necessary
- Alendronic acid may be tried for pain/ deformity
Characteristic Paget's disease X-ray changes: sclerotic bone, course trabeculae, thickend cortex, sabred tibia
Longmore M, Wilkinson I, Turmezei T, Cheung CK (2009). Oxford Handbook of Clinical Medicine (Seventh Edition) Oxford University Press, Oxford, pp.841
Martini FH (2006) Fundamentals of anatomy and physiology (Seventh Edition). Pearson Benjamin Cummings, San Francisco. pp.1109
"Osteoporosis", Wheeless' Textbook of Orthopaedics:
"Osteomalacia", Wheeless' Textbook of Orthopaedics:
"Paget's Disease", Wheeless' Textbook of Orthopaedics:
"Looser's Zone", General Practice Notebook:
Lumbar spine XR from:
Fractured neck of femure XR from:
Rickets and Looser's zone images from:
Paget's XR from: