Osteoporosis means thin bone and the term implies a reduction in bone mass including all components of bone and not just calcium. It is already a major problem; it is said that 40% of Caucasian women and 20% of men will suffer fractures as a result of osteoporosis. The risk in women will triple as a result of increasing life expectancy. One-third of women will have had a fracture by the age of 90 years.
Changes in bone mass with age are shown. Bone mass increases up to the age of puberty and remains stable until the menopause. After the menopause, there is a progressive reduction as a result of oestrogen deficiency. The rate of reduction in bone mass is much less in men. When bone mass falls below the fracture threshold, there is a risk of fracture, which is increased in the elderly by other factors such as failing eyesight, incoordination and falls.
RISK FACTORS AND CAUSES
Osteoporosis is not a disease but a condition which exists to a variable extent as a result of a number of different factors, shown. The most important risk factors are age and sex: osteoporosis has its biggest impact in postmenopausal women.
TYPES OF OSTEOPOROSIS
There are two types of osteoporosis: type 1 the typical postmenopausal osteoporosis and type 2 the more recently recognised senile osteoporosis which occurs in the over-seventies. Their features are summarized. Four factors are thought to be important in the pathogenesis of type 2 osteoporosis:
1 Less sunshine.
2 Lower calcium intake.
3 Less vitamin D-containing foods.
4 Less vitamin D synthesis in the skin.
Increased parathyroid activity is the result, leading to cortical bone resorption.
Osteoporosis is not itself painful. The pain results from fractures and is usually therefore self-limiting although long-standing pain can result from structural problems, for example as a result of vertebral crush fractures. The typical history in osteoporosis of the spine is thus an episode of very severe pain in the dorsal spine which resolves lowly over the course of about 6 weeks. Fractures can also occur in the lumbar spine. The typical sites of fractures in osteoporosis are vertebrae, the distal radius (Colles fracture) and the neck of the femur. Other symptoms which result from vertebral osteoporosis are loss of height, increasing kyphosis and abdominal protruberance. Similar symptoms can occur in such conditions as multiple myeloma and metastatic deposits.
X-RAYS will demonstrate most fractures. Bone scans are sometimes useful to demonstrate a recent fracture and to distinguish an osteoporotic crush fracture from ametastatic lesion. These often appear identical on Xray but metastatic lesions are likely to be associated with multiple lesions elsewhere. X-rays are however of limited value in diagnosing osteoporosis itself because the whiteness of the bone depends on the penetration of the film.
SERUM CALCIUM, PHOSPHATES AND ALKALINE PH0SPHATASE are usually normal. Osteoporosis is not a disorder of calcium metabolism.
HISTOLOGICAL EXAMINATION of a bone biopsy mayoccasionally be required to confirm the diagnosis.
BONE DENSITOMETRY (DEXA SCANNING) is of increasing importance in screening people at risk and in monitoring the effects of treatment.
ApPROPRIATE INVESTIGATIONS to exclude diseases that are associated with osteoporosis are shown.
Treatment of the established disease is unsatisfactory because bone mass has already been lost. Prophylaxis for high-risk individuals is, therefore, preferable. Elderly patients should be educated about the risks of falling.
FRACTURES should be treated by conventional orthopaedic means. Fresh fractures of the spine require short-term bed rest with adequate analgesia and, if necessary, muscle relaxants.
Prevention of osteoporosis IS Important, particularly in postmenopausal women and in the elderly. The following measures are used:
OESTROGEN THERAPY is of proven value and is being increasingly used as evidence accumulates that the potential side-effects (thrombosis, endometrial carcinoma, hypertension) are less than the benefits. Those with premature menopause or ovariectomy, those with high-risk factors, e.g. nullipara, the hypogonadal, those with family history of osteoporosis, should certainly be treated and many believe hormone replacement therapy (HRT) should be given to most postmenopausal women.
It is now clear that androgens should be given to hypogonadal men, though prostatic hypertrophy is a problem.
DIETARY CALCIUM should be increased to above 1.5 g daily (40 mmol Ca2+), especially for postmenopausal women, with or without vitamin D supplements. This gives a small benefit. Vitamin D is necessary for housebound elderly people.
COURSES OF DIPHOSPHONATES which inhibit bone resorption may be used and seem to be safe.
MODERATE EXERCISES AGAINST GRAVITY, e.g. walking, running and competitive sports, also retard bone loss and should be encouraged.
FLUORIDE increases bone density but is difficult to use and is not recommended.
CALCITONIN AND PTH remain under investigation and the field is changing rapidly. Paget’s disease
DEFINITION AND CAUSATION
Strictly this is a disorder of bone remodelling rather than a metabolic bone disease, although the metabolic changes are considerable. Recent evidence involving apparent viral inclusion bodies suggests a possible ‘slow viral’ aetiology, for which canine distemper virus is a prime candidate. The condition causes uncontrolled bone turnover with local excessive osteoclastic resorption followed by disorded osteoblastic activity leading to abundant new bone formation which is structurally abnormal and weak.
It is a common disorder, most often seen in Europe and particularly northern England, affecting up to 10% of adults by the age of 90 years, though rarely before the age of 40 years. It is relatively rare in North America, Africa and Asia. Probably less than 2% of those affected show any symptoms.
SITES OF INVOLVEMENT AND CLINICAL
The commonest sites are the femur, pelvis, tibia, skull and lumbosacral spine, although any bone can be involved. Most cases are entirely asymptomatic, but features include:
• Bone pain, usually spine or pelvis
• Apparent joint pain, when involved bone is close to a joint
• Deformities, particularly bowed tibia and skull changes
• Complications, e.g. deafness due to nerve compression, a high-output cardiac state from shunting, fracture through abnormal bone and, rarely, osteogenic sarcoma.
RADIOLOGY AND SCANNING
Characteristic changes are seen most often in the pelvis, skull or spine involving resorption fronts, osteolytic lesions, sclerosis and thickening of bone trabeculae, long bones and vertebrae. Bone scans will show the extent of skeletal involvement, often including unsuspected areas, but may be difficult to distinguish from metastatic carcinoma, sometimes a major clinical differential diagnosis.
The hallmark of Paget’s disease is an increased serum alkaline phosphatase with normal serum calcium and phosphate, reflecting the increased bone turnover . The serum alkaline phosphatase levels may exceed 1000 mU litre.”. The levels are normal only when bone involvement is limited. Mild hypercalcaemia only follows immobilization. Bone turnover can also be monitored by 24 hour urinary hydroxyproline excretion, which is frequently increased.
When asymptomatic, Paget’s disease requires no therapy. Pain is the usual indication for treatment: SIMPLE ANALGESICS OR NSAIDs are sometimes adequate.
DIPHOSPHONATES, most often disodium etidronate 5 mg kg:’ daily over 3-12 months, will reduce osteoclastic activity and frequently induce remissions of up to 2 years. Diphosphonates are pyrophosphate analogues which are resistant to enzymatic hydrolysis. Serum alkaline phosphatase activity frequently falls, reflecting the effect of the drug. Disodium etidronate must be given away from meals as absorption is erratic, and higher doses may lead to osteomalacia. CALCITONIN (salmon or porcine) 50IU three times weekly to 160 IU daily inhibits bone resorption and turnover, but is extremely expensive and the sideeffects of flushing and nausea are frequent problems. Antibody formation is a further difficulty.
SEVERE CASES may benefit from courses of intravenous diphosphonates under specialist supervision.
MITHRAMYCIN is very occasionally used in severe cases.
The dose is 10-15 JLgkg:’ i.v. and requires monitoring of platelets and liver biochemistry.