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Relating the results of our investigations to the knowledge hitherto acquired about the etiology of osteoporosis (which I have already referred to), I am inclined to interpret the pathogenesis of osteoporosis in the following way: 1)
Osteoporosis may therefore be the consequence either of a congenital osteoblastic deficiency, such as that found in cases of osteogenesis imperfecta, or of reduced osteoblastic activity due to absence of trophic stimuli such as mechanical stress and the sex hormones, or of reduced activity of the bone cells due to anti-anabolic substances which inhibit them, such as cortisone and its derivatives and the thyroid hormone in strong doses, or lastly of reduced availability of construction material due to its introduction in reduced quantities (starvation, dysfunction of the digestive system) or due to hindering of synthesis (deficiency of vitamin C, diabetes, cortisone and its derivatives) or due to an excessive degree of destruction (thyrotoxicosis). In the case of anti-anabolic hormones from the adrenal cortex, the mechanism may thus be twofold: inhibition of the osteoblasts and deprivation of the osteoblasts of glucoprotein material due to a general anomaly of metabolism. This may perhaps explain the most serious forms of bone atrophy which are usually observable in cases of hyperfunction of the adrenal cortex.
Senile osteoporosis should, in my opinion, be included in the first of our groups because it cannot be said to be brought about by any of the causes usually cited for osteoporosis– such as deficiency of sex hormones, excess of hormones from the adrenal cortex, deficiency of calcium, etc.–and in all probability it will depend on a progressive involution of the osteoblasts brought about by old age.
Senile involution is an expression of the descending phase of life's parabola and it involves all the organs and all the parenchymatous tissues in the human body, but it does not cause a parallel reduction of functions and activities on all of them equally. The skeletal system is one of the first to feel these reductions, because in old age life necessarily becomes less intense. Consequently in the economy of the ageing subject the generally reduced level of metabolism brings about a sort of selection in the nourishment of the different organs and systems, and sometimes almost a dismantling of some of these in an attempt to fall in with the new and reduced level of activities of some of the parenchymatous tissues, activities which may be incomplete or even transferred elsewhere. We believe that the moment which originally determines the beginning of senile osteoporosis coincides with the involutional process of cellular metabolism that strikes at all parenchymatous tissue during old age–striking, in the case of osteoporosis, hardest of all at the bony tissues.
There is, indeed, no doubt that certain essential processes of cellular metabolism do alter with age, and that the reduction in the activity of the gonads does have considerable importance. In any case, just as adolescence and old age cannot be explained only in terms of gonadal activity, so the involution of the skeleton cannot be due merely to the involution of the gonads. How should one then interpret the well known benefit afforded by administration of sex hormones in cases of osteoporosis? Probably the action of oestrogens and androgens is, in this case, of a pharmacological nature, and comparable, for instance, to the action of digitalis on the cardiac muscle. It will be remembered how digitalis acts almost exclusively on myofibrils which have become inadequate, and has little or no effect on a normal myocardium. Similarly, the sex hormones would seem to exert a stimulating action on osteoblasts that are on the way to involution, while they exert little or no action on normal osteoblasts. In support of this we have the findings of Urist and other workers, who demonstrated that the administration of sex hormones produces calcium and nitrogen retention only in osteoporotics, while in non-osteoporotic subjects of the same age it produces no effect. On the other hand, the action of the sex hormones might act in cases of senile osteoporosis by returning the changed level of protein metabolism to normal.
From the data in the literature and from the results of our own investigations, I conclude that osteoporosis in general, and senile osteoporosis in particular, are first and foremost the result of a disturbance in the metabolism of bone, and that the metabolic disturbance is closely and exclusively related to the degree of activity and the state of activity of the cells in the bone. Lastly, I believe that senile osteoporosis should not be considered an actual disease but rather as one limited aspect of the normal descending parabola which affects to a greater or less degree all the tissues of the body.
1. Individuals who are normal and not osteoporotic seem to show retention of cortical bone at successive decades of life in proportion to the total lean body-mass. In patients with osteoporosis the weight of the skeleton decreases at a rate exceeding the physiological rate of atrophy of muscle, tendon and bone tissue that occurs with the time-dependent process of ageing.
2. Six patients representing the typical forms of osteoporosis commonly found in orthopaedic practice were investigated intensively over a period of three years and compared with individuals in whom there was no osteoporosis by studies of metabolic balance, Sr85 osteograms, and tetracycline deposition.
3. Studies of metabolic balance in patients with osteoporosis showed normal or negative calcium balances, but an equilibrium for the metabolism of nitrogen and phosphorus. Increased intake of calcium in the diet produced retention of calcium but not sufficient phosphorus, nitrogen or gain in weight to prove that the patient had made new bone and healed the osteoporosis.
4. Radio-isotope osteograms showed high, normal or low rates of change of uptake of Sr85 and the accretion rate was calculated to be normal or low in individuals with osteoporosis. High uptake of tetracycline by a small mass of bone tissue and by a relatively small percentage of the total number of osteons suggested that in an adult human being the calcium reserve in the skeleton is enormous. Thirty to 50 per cent of the total bone mass was sufficient to turn over 0·5 to 1·0 gramme, the amount of calcium utilised in twenty-four hours by the human adult. This was accomplished by structural or old bone throughout the entire skeleton, and by labile or newer bone located in approximately 10 per cent of the total number of Haversian cylinders or osteons.
5. Some of the unclosed or half-closed osteons were hyperactive in osteoporotic bones. In the process of remodelling of cortical bone a significant quantity of bone tissue was incompletely restored and there were, presumably as a result, intermittently large or small negative calcium balances. Osteoporosis may have been the cause, rather than the result, of the negative calcium balance.
6. The experimental and clinical literature of the past ten years, and studies on patients described in this critical review, were interpreted to indicate that prolonged calcium deficiency, castration, hyperadrenal corticoidism or a sedentary life may precipitate, accentuate and accelerate osteoporosis in individuals who are genetically predisposed to develop it. Sometimes high calcium intake or sex hormones, or both, may have slowed the rate of resorption but did not replace the deficit in cortical bone.
7. Further research is necessary to find the chief etiological factor and to produce the cure for this increasingly common disorder of the skeleton.
1. Discs of bone from two fixed sites on the front of the femur were taken from ninety-one necropsy subjects and the density, width and histological appearance of the cortical bone were examined.
2. Cortical thickness, and the density of the femoralcortex, decreased with increasingage of bone.
3. There was an increase in the rate of resorption of the bone cortex from both sexes after the fifth decade.
4. The difference between the density of the metaphysial cortex and that from the diaphysis increased for both sexes after the age of fifty, because of the greater metaphysial resorption.
5. There was no change in the degree of mineralisation of the cortical bone with age. The decrease in density with age is, therefore, accounted for by resorption.
1. The appearance of decalcified bone matrix in the electron microscope is described.
2. In the matrix two types of collagen fibril have been distinguished. Differences observed are in solubility, x-ray diffraction pattern and appearance. In infant bone the form which appears as fine fibrils predominates. In adult bone the form which appears as tubular fibrils of larger diameter predominates.
3. In bones from elderly subjects the chemical reaction employed to convert collagen into eucollagen sometimes hydrolyses fatty acid esters, and lines due to the free fatty acid are found on the x-ray diffraction patterns of the insoluble residue after citrate extraction.
4. In ancient bones and fossils the stable tubular form of collagen survives, but not the fine fibrils.
5. When decalcified, the matrix in osteoporotic bones loses its architecture and fibrillar form. Under conditions in which only a small fraction is dissolved from normal bone most of the collagen in osteoporotic bone disperses in citric acid. The insoluble residue then gives a modified x-ray diffraction pattern.
6. Evidence has been produced to suggest that the immediate cause of many forms of osteoporosis is some local factor affecting the osteocytes, rather than a general chemical effect.
1. Recently described histological and radiographic methods of diagnosing osteoporosis have been applied to patients with transcervical and intertrochanteric fractures of the femur.
2. Both methods indicate a higher incidence of osteoporosis in such patients than in a control series, especially in older women with intertrochanteric fractures.
3. A discrepancy between the results of biopsy and radiographic examination was encountered, the explanation of which is not yet clear.
A study of a collected series of femoral neck fractures in seventy-one children observed for one to nineteen years shows:
1. This injury is rare but occurs in children of all ages from three to sixteen years old.
2. The fractures may be classified as transepiphysial, transcervical (the commonest), basal and pertrochanteric. Displacement was frequent.
3. The fracture usually followed severe violence, especially falls from a height or motor accidents.
4. Complications were frequent and included avascular necrosis, delayed union (seventeen cases), non-union (seven cases) and disturbances of growth at both the upper and lower ends of the femur.
5. Avascular necrosis occurred in thirty patients (42 per cent). Three patterns of necrosis are described : diffuse, localised and confined to the femoral neck. The radiographic appearances of avascular necrosis after this fracture are different from those of pseudocoxalgia (Legg-Calvé-Perthes' disease).
6. Non-union did not occur after adequate primary internal fixation or after primary subtrochanteric osteotomy.
7. The management of an undisplaced fracture presented no great problem and the results were good. A plaster spica is recommended for treatment of this fracture. Exceptionally, avascular necrosis developed.
8. Treatment of the displaced fractures (forty-nine cases) was less satisfactory. A good result was obtained from primary treatment in only fifteen patients.
9. The value of different methods of primary treatment is discussed, including manipulative reduction and immobilisation in a plaster spica, manipulative reduction and internal fixation, and primary subtrochanteric osteotomy. Manipulative reduction and immobilisation in a plaster spica is not recommended.
10. Salvage operations were required in nineteen patients. Late subtrochanteric osteotomy is of value in the management of some of these problems.
1. Aching pain in the thigh, hip or buttock in an elderly person should lead to radiological examination of the hip region. In patients who have been subjected to irradiation for pelvic neoplasms a spontaneous fracture should be strongly suspected and the patient kept under close review, even if the first radiograph is negative.
2. Patients with spontaneous fractures of the femoral neck can be satisfactorily treated by Smith-Petersen nailing even when symptoms have been present for as long as sixteen weeks and displacement for eight weeks. Osteotomy is unnecessary if adequate reduction can be obtained.
Eighty patients who sustained a fracture of the floor of the acetabulum are reviewed, and the mechanism of the injury was investigated by clinical and experimental studies. The results of the injury in fifty patients are presented, with an account of the three clinical types of acetabular fracture.
A case of osteochondritis dissecans complicating Legg-Calvé-Perthes' disease is reported. Despite four years of conservative treatment in an ischial-bearing caliper a part of the fragmented femoral head failed to unite with the rest of the epiphysis and has persisted as an intra-articular loose body.
Freehafer (1960) listed the indications for surgical removal of this fragment in such cases: 1) persisting symptoms; 2) dislocation of the loose fragment into the joint with secondary arthritic changes inevitable; 3) a mechanical block to movement of the hip.
Since our patient had a relatively symptomless hip with a full range of movement, surgical removal of the loose body was not advised. The prognosis for this hip is nevertheless guarded, and surgery can be reserved for the above indications or for reconstructive procedures should they be required in the future.
1. An account is given of a family in which five members in three generations were affected by osteochondritis involving the hips, in three cases bilaterally.
2. One patient showed aseptic osseous necrosis of the epiphyses of the ankles and fingers.
3. The differential diagnosis between Perthes' disease and multiple epiphysial dysplasia is discussed, but it is not certain into which category these patients fall.
4. The assistance of a family history and skeletal survey in diagnosis is illustrated.
1. The occurrence of bilateral double-layer patellae in association with multiple epiphysial dysplasia is described in three siblings.
2. Twelve cases of bilateral double-layer patellae have been reported previously, and in all there was an accompanying skeletal dystrophy which, although not diagnosed as such, is likely to have been multiple epiphysial dysplasia.
3. It is suggested that although they occur only in a minority of cases, double-layer patellae when present are a feature of considerable diagnostic value in multiple epiphysial dysplasia. Lateral radiography of the knees may therefore be of assistance in the diagnosis of multiple epiphysial dysplasia.
1. Forty-eight paralytic dislocations of the hip have been studied and twenty-seven operations for correction of valgus deformity of the femoral neck have been done.
2. The differing features of dislocations occurring in poliomyelitis, cerebral palsy and meningomyelocoele are considered in relation to management after operation.
3. Early recognition of subluxation is essential to a successful varus osteotomy. An angle of 105 degrees rather than the 120 degrees previously recommended is advisable for children under the age of five.
4. Redislocation is most likely to occur in meningomyelocoele in which muscular imbalance is greatest, and in later cases where the acetabulum has become shallow by growth without the femoral head within it. It has not occurred as a late complication after weight bearing has been established, from a recurrence of valgus deformity.
The Brittain V-arthrodesis is a satisfactory procedure for osteoarthritis of the hip. It is particularly suitable for elderly patients when the range of hip flexion is less than 60 degrees. If the four deaths are excluded, two-thirds of the patients secured a sound bony fusion. This occurs slowly. All but one of the patients who survived for three years or more after operation had a sound bony fusion. It is evident that the operation, given time, yields a high rate of sound bony fusion in the hip. It seems likely that use of the McLaughlin nail plate would prevent the one serious complication, namely fracture of the shaft of the femur through or immediately below the drill hole made for the fibular graft.
1. Surveys of a working community, of a group of elderly people, and of an urban population show an incidence of Dupuytren's contracture among men varying from 0·1 per cent in the age group fifteen to twenty-four, to 18·1 per cent in those aged seventy-five and over; and among women from 0·5 per cent in the age group forty-five to fifty-four, to 9 per cent over seventy-five. It is estimated that in the population aged fifteen and over in Lancashire and Cheshire there will be 4·2 per cent of the men and 1·4 per cent of the women with some degree of palmar contracture.
2. There appears to be no relationship between the type of occupation and the incidence or severity of contracture in men, except that among those engaged in light manual work the proportion of mildly affected hands is higher, and of bilateral contracture lower, than among either non-manual or heavy manual workers.
3. Evidence is provided that rheumatoid arthritis, past polyarthritis, osteoarthritis, cervical spondylosis and Paget's disease occur no more often in those with Dupuytren's contracture than in other members of the community.
4. Examination of the patients in an epileptic colony confirms a strong association between Dupuytren's contracture and epilepsy. Knuckle-pads, plantar nodules and periarthritis of the shoulder are all more frequent in epileptic than in non-epileptic patients with Dupuytren's contracture. Epileptics also show a higher proportion with bilateral contractures and a greater tendency to a symmetrical pattern of contracture in the two hands. A strong constitutional factor, probably genetic, thus operates in persons with both diseases.
Nevertheless, the frequency of a positive family history of contracture is lower in the epileptic cases, and reasons for this are discussed.
5. From the limited material available in the literature there would appear to be an inverse relationship between the population of certain countries and the prevalence in them of Dupuytren's contracture. The possible significance of this is briefly discussed.
1. The age of the patient has no influence on the incidence of non-union in fractures of the forearm in adults.
2. The degree of displacement of the fracture is an important factor in non-union, and is related to the violence of the injury.
3. Fractures of one bone unite better than fractures of both bones, and this is due to the stabilising effect of the intact bone.
4. Open and comminuted fractures have a much higher incidence of non-union.
5. The lowest incidence of non-union, allowances being made for other significant factors, was in cases treated conservatively; and after that in cases treated by plating followed by immobilisation in plaster.
6. Plating without subsequent immobilisation in plaster is a method to be abandoned, but there is some advantage in waiting for ten days, until post-operative oedema has been absorbed, before applying the plaster.
7. In cases in which several factors predisposing to non-union are present in the same patient, it seems justifiable to supplement plating by cancellous onlay strips as a primary procedure.
8. In cases of non-union the cancellous insert graft described by Nicoll succeeded in 94·5 per cent of the cases, many of which were exceptionally difficult problems. In 75 per cent union occurred within four months of grafting.
9. The restoration of mobility, either after union of the fracture or after grafting operations, was never a serious problem in the present series.
1. Two cases are reported showing the syndrome of chondrodysplasia, manual polydactyly, ectodermal dysplasia affecting the teeth and nails, and congenital heart disease.
2. Particulars of thirty-eight cases are tabulated, and the features of the syndrome are discussed.
3. The syndrome is regarded as showing an autosomal recessive mode of inheritance.
Since this paper was submitted for publication three additional reports have appeared, two of which represent typical examples of the syndrome. Husson and Parkman (1961) reported the case of a female infant dying at the age of four months with chondroectodermal dysplasia, obliteration of the upper labiogingival sulcus, and congenital heart disease. The heart lesions included anomalous pulmonary venous return, single atrium and a persistent left superior vena cava. There was no known consanguinity. In reviewing the cardiac lesions described in chondroectodermal dysplasia they include another case with anomalous pulmonary venous return described by Darling, Rothney and Craig (1957), which also showed chondroectodermal dysplasia and polydactyly, though details of the extracardiac malformations are not given. Nabrady (1961) described a four-year-old Hungarian girl with ectodermal defects involving the teeth and nails but not the hair, polydactyly, distal shortening of the extremities producing dwarfing, and typical radiological appearances of the long bones. There was presumptive evidence of a septal defect of the heart. There was no consanguinity, but the mother was considered to show a "forme fruste" of the condition. A necropsy report by Meitner (1961) of a newly born premature infant with multiple congenital malformations of organs of ectodermal, mesodermal and endodermal origin is of interest because these malformations included extreme polydactyly of hands and feet, absence of nails, chondrodysplasia, and trilocular heart. In many respects, however, the case is atypical of chondroectodermal dysplasia.
1. Four out of five patients with spondylolisthesis, four-fifths of whom were seen at least five years after operation, had their symptoms relieved after posterior spinal fusion.
2. In a small series of patients treated by anterior spinal fusion, the results were less successful.
1. A simple model embracing both the hind and forefoot is described.
2. From this model the expected results of various methods of correcting the pronated foot can be deduced, and these were confirmed by human experiment.
3. It is indicated that a permanent correction requires a biological modification of foot posture achieved by mechanical means.
Two cases of intraosseous glomus tumour of a terminal phalanx are described and the literature is reviewed.
1. A case of essential osteolysis previously reported in this Journal is recalled briefly and its subsequent course is outlined.
2. A successful prosthesis is described which has enabled the patient to lead a relatively normal life.
1. The "halo" traction apparatus and its method of application are described in detail.
2. Its use in nine patients with subluxation or fracture-dislocation of the cervical spine, and in one patient with extensive vertebral disease, is recorded.
3. The indications for using the "halo" traction apparatus are outlined.
1. By the use of a device that allows movement of a human finger joint to take place uninfluenced by muscle activity, the coefficient of friction has been determined between living articular surfaces.
2. The force of friction rises as the range of movement is increased, because of the tension then developing in the ligaments and the soft tissues surrounding the joint.
3. Measurements have also been made of the forces of friction within the ankle joint of the dog and within four types of reciprocating bearings (plastic, oil-lubricated, "floating" and hydrostatic).
4. By altering the load borne by the joints and bearings it has been shown that joints resemble in their behaviour those bearings in which a film of fluid is maintained between the fixed and moving surfaces, rather than bearings depending wholly or in part on boundary lubrication.
5. It is suggested that joints normally owe their great freedom of movement to a special type of fluid film lubrication that has been termed "weeping lubrication," supplemented by "floating lubrication," though on occasions boundary conditions may prevail.
1. A study has been made of the repair of bony defects in the calvaria of albino rats.
2. An accelerated rate of bone repair was observed in experimental defects into which chondroitin sulphate-treated demineralised bone was implanted.
3. Acid-soluble collagen reconstituted with chondroitin sulphate was also more effective as an implant than was acid-soluble collagen reconstituted with sodium chloride.
4. It is concluded from these studies that chondroitin sulphate treatment accelerated the rate of new bone formation induced by demineralised bone, by reconstituted acid-soluble collagen, and to a lesser extent by Gelfoam. It was also found that demineralised bone and fresh homogenous bone promoted bone repair, but that chondroitin sulphate-treated demineralised bone promoted the most rapid rate of bone repair among the substances tested.
5. The possible role of chondroitin sulphate in bone formation is discussed.
1. The response of the first regional lymph node to a homograft of fresh iliac cancellous bone inserted subcutaneously into the rabbit's ear three weeks after the introduction of a similar graft from the same donor into the same ear has been investigated in thirty rabbits. Fifteen rabbits which received second-set autografts of cancellous bone have also been studied.
2. The insertion of second-set homografts of fresh marrow-containing cancellous bone evokes an immune secondary response in the lymph nodes draining the grafts.
3. The increase in weight of the first regional lymph nodes on the side receiving second-set homografts is more rapid and of greater magnitude than that of nodes draining first-set homografts of cancellous bone. Second-set autografts evoke weight changes in the draining nodes similar to those in nodes draining first-set autografts of cancellous bone.
4. The histological changes which occur in the lymph nodes draining the second-set homografts (secondary response) are described and compared with those occurring in lymph nodes draining first-set homografts of cancellous bone (primary response).
5. In the primary response the distribution of large and medium lymphoid cells is throughout an activated sector of the cortex of the lymph node (Burwell and Gowland 1961), but in the secondary response these cells are found peripherally within the activated sector of the node. In both the primary and the secondary responses large and medium lymphoid cells are found in the medullary trabeculae of the lymph nodes.
6. The differences between the primary response of lymph nodes draining a tissue homograft (cancellous bone) and the primary response of lymph nodes draining classical antigens, and reported by other workers, are described.
7. Knowledge concerning the inflammatory response in the tissues of the host surrounding homografts of fresh cortical and cancellous bone implanted into animals previously sensitised to tissue from the respective donor is reviewed.
8. The late phase of new bone formation by homografts of fresh cancellous bone is discussed in the light of immunological studies.
1. The effects of heavy training on a skeletal muscle have been studied in the rat. After denervation of the triceps surae muscle the tendon of the plantaris muscle was implanted into the tuberosity of the calcaneum. It was then possible to demand an unusual performance of the plantaris, the weight of which is only 18 per cent of the weight of the triceps surae.
2. Formation of new muscle fibres was observed after prolonged heavy training. This is incontrast to the opinion of most investigators, who have seen no new fibres formed after training. Degenerative changes followed by regeneration were also seen.
3. The trained muscle could almost double its weight, and treble its force. Paradoxically, the supposedly non-contractile sarcoplasm was seen to have increased after training.
4. Training induced a strong protein synthesis in muscle. In normal muscle protein synthesis can hardly be demonstrated.
5. Connective tissue grew between single muscle fibres in the heavily trained muscle. Its distribution was unequal.
6. Heavy exercise caused marked swelling of an untrained muscle.
7. Functional recovery was satisfactory after the operation. This showed that a muscle can be replaced by one only one-fifth its weight, provided the latter is trained adequately.
8. Not even the most arduous training could inflict permanent damage on the muscle.
Experiments on white mice were undertaken to determine the reaction of bone to the intramedullary introduction of the virus of tick-borne encephalitis. The following conclusions were drawn.
1. The tick-borne encephalitis virus S47, when introduced intraosteally in white mice, provokes osteitis.
2. Inflammation may lead to acute necrosis of bone, preceded by marked medullary oedema and subsequent proliferation, or it may take a milder form with haemorrhagic effusion into the marrow tissue and subsequent hyperplasia of connective tissue.
3. Damage to the epiphysial and articular cartilage may ensue in the course of acute necrotic osteitis.
4. Skeletal and extra-skeletal osteogenesis is a characteristic feature of viral osteitis.
5. In radiographs in acute viral osteitis with extensive necrosis the expanded bone appears to be thickened.
6. Viruses of the S47 strain introduced intraosteally preserve their affinity for brain tissue after three passages through bone.
7. Viruses introduced into the bony tissue preserve their toxicity and are found in the bony tissue after ten days in quantities lethal for young mice when inoculated intracerebrally.
8. The tick-borne encephalitis virus S47 is pathogenic when inoculated into the marrow in white mice.
9. In osteitis of non-bacterial origin in man the possibility of viral infection should be considered.
The oldest texts describing infantile paralysis (Underwood's 1789 and Salzmann's 1734) are reviewed and discussed. Salzmann's case report is likely to be a description of acute anterior poliomyelitis and is documented by details of the history, clinical picture and postmortem findings.
