Family History
A maternal history of hip fracture increases the risk of hip fracture in an individual.
Osteogenesis Imperfecta
Late- onset forms (e.g. Sillence type I) may present with vertebral fracture. The clinical clues are the blue sclerae, hypermobile joints, lax skin, cardiac murmurs, and deafness.
Environmental Factors
Cigarette Smoking and Chronic Obstructive Pulmonary Disease
Smoking results in lower oestrogen levels and early menopause, and smokers often have a slender stature (see next). Chronic lung dis ease is associated with chronic respiratory acidosis and decreased physical activity.
Alcohol Abuse
The relationship between alcohol and bone loss is complex (and there may even be a protective effect at a low level of intake). Alcoholism results in low BMD because of poor nutrition and pseudo- Cushing’s syndrome, and a direct suppressive effect of alcohol on osteoblasts. Fractures result from the increased propensity to fall.
Physical Inactivity and Immobilization (Neurological)
Athletes have high BMD. However, bone loss only results from complete immobilization (or space flight). The bone loss after paralysis (e.g. stroke) is regional.
Thin Habitus
This is a risk factor for fracture through decreased oestrogen pro duction from adrenal androgens (in adipose tissue) and through decreased padding (to cushion a fall). Women with hip fracture weigh about 8 kg less than the average woman.
Diet— Low Dietary Calcium
Low dietary calcium and high dietary sodium are considered risk factors for osteoporosis. Calcium requirement increases during growth and in the postmenopausal period. A postmenopausal woman should take 1500 mg/ day of calcium.
Little Exposure to Ultraviolet Light
Ultraviolet light (UVB) acts on the skin as the main source of vitamin D. The housebound are liable to vitamin D insufficiency. This does not result in clinical osteomalacia, but the decreased calcium absorption (see earlier) results in secondary hyperparathyroidism.
Menstrual Status
Early Menopause
A menopause before the age of 45 years is associated with increased risk of fracture. A menopause before the age of 40 years is often associated with some endocrine cause and should be investigated further.
Amenorrhoea
A late onset of the menarche and periods of amenorrhoea of any cause (e.g. exercise related, are associated with decreased bone mass later in life).
Anorexia Nervosa
This is associated with bone loss and increased risk of fracture. The bone loss is probably irreversible after 4 years of amenorrhoea. The mechanism of the bone loss is not just oestrogen deficiency. The diet is low in calcium and serum IGF- 1 levels are low, and cortisol secretion may be increased.
Hyperprolactinaemia
This results in oestrogen deficiency. Not all studies have reported bone loss, and it may be that prolactin has some beneficial effects on calcium homeostasis, such as an increase in calcium absorption.
Drug Therapy
Corticosteroids
In the United Kingdom, over 250 000 patients take continuous oral glucocorticoids, yet no more than 14% receive any therapy to prevent bone loss, a serious complication of glucocorticoid treatment. Bone loss is rapid, particularly in the first year, and fracture risk may double. The mechanism of the bone loss is mainly a suppression of osteoblast activity. This differs from oestrogen deficiency, in which the mechanism is mainly increased activation frequency. A treatment algorithm has been presented for adults receiving glucocorticoid doses for 6 months or more. General measures (e.g. alternative glucocorticoids and routes of administration) and therapeutic interventions such as bisphosphonates, are re commended.
Antiepileptic Drugs
Phenobarbitone and phenytoin are known to affect vitamin D metabolism and result in osteomalacia. More commonly, they may cause secondary hyperparathyroidism and osteoporosis.
Excessive Substitution Therapy
Thyroxine doses sufficient to suppress thyroid- stimulating hormone, and hydrocortisone doses that result in 24- h urinary free cortisol above the reference range, have adverse effects on bone turnover and bone density.
Anticoagulant Drugs
Heparin stimulates bone resorption by a direct effect on osteoclasts. Its long- term use (e.g. in pregnancy) results in bone loss at the spine and hip of 8– 10% over 6 months. Warfarin may interfere with the γ- carboxylation of bone proteins, and its use is associated with an increased risk of fracture.
Endocrine Diseases
Primary Hyperparathyroidism
This is associated with an increase in bone turnover and a decrease in bone mass, particularly at sites rich in cortical bone. It is likely that there is an increase in fracture rates. These changes are reversible with surgical removal of the tumour.
Thyrotoxicosis
Cushing’s Syndrome
Cushing’s disease may present with vertebral fracture. The bone loss in the first few years after pituitary surgery is between 10% and 20% at the spine.
Addison’s Disease
This is associated with decreased bone mass, resulting from excess substitution therapy and deficiency of adrenal androgens (precursors for oestrogen synthesis in men and postmenopausal women).
Haematological Diseases
Multiple Myeloma
This may present with vertebral fracture. It is usually identified with serum protein electrophoresis, and urinary Bence Jones testing, but occasionally the myeloma may be non- secretory and can usually be diagnosed by bone marrow examination.
Systemic Mastocytosis
This may cause decreased or increased bone density. It can be identified by urticaria pigmentosa, and mast cells are identified in the bone biopsy.
Pernicious Anaemia
This has been associated with low bone density and increased risk of fractures. The mechanism is unclear, as the absorption of calcium from food is normal despite the absence of gastric acid.
Rheumatological Diseases
Rheumatoid Arthritis and Ankylosing Spondylitis
The immobility may be an important cause, as may be the local (and circulating) cytokines, which promote bone resorption. The corticosteroid therapy for rheumatoid arthritis may also contribute.
Gastrointestinal Diseases
Malabsorption Syndrome
Diseases such as coeliac disease may present with osteoporosis. Other inflammatory bowel diseases, such as Crohn’s disease, may require treatment with corticosteroids. Patients who have had peptic ulcer surgery have low bone density and increased risk of fracture. This may also be due to their habits— such patients are usually thin, commonly smoke, and may take excess alcohol.
Chronic Liver Disease Chronic obstructive liver diseases, such as primary biliary cirrhosis, are associated with osteoporosis. Bilirubin has been associated with osteoblast suppression in vitro. Liver transplantation results in further bone loss and about one- third of patients suffer fractures. This bone loss is likely to be related to the immunosuppression (corticosteroids and cyclosporine).
