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THE CLASSIC: Osteoporosis

2006; Lippincott Williams & Wilkins; Volume: 443; Linguagem: Inglês

10.1097/01.blo.0000200246.45178.fe

1528-1132

Arthur Steindler,

Bone health and osteoporosis research

Arthur Steindler (1878-1949) was a polymath. He spoke six modern languages fluently and in also had a classicist's knowledge of Latin and Greek. He had advanced training in mathematics and engineering. He was a skilled musician and was remarkably well versed in literature and the humanities. He also had a long and distinguished career in orthopedic surgery. Dr. Steindler was born in Vienna and taught in the rigorous Austrian and German educational systems in the late nineteenth century. He earned his degree in medicine at the University of Vienna in 1902 at the age of 24 years old. Because he came from an affluent family in Vienna, a successful career in medicine seemed to be his for the asking. However, he decided against the political, economic, and social structure of the Austro-Hungarian Empire and came to the United States in 1907. After working as an orthopedist in Chicago, IL for a few years, he moved to Iowa City, IA in 1913 where he immediately immersed himself in the establishment of a medical college at the state university there. After the accreditation of the college was secured, Dr. Steindler, by now a professor at the university, began working toward the creation of a department of orthopedics. He achieved this goal by 1925 and served as Chairman for nearly 35 years. Those who knew him remark about his legendary generosity and hospitality as well as about his hard work, energy, and high achievement. This classic article on osteoporosis reflects the thoroughness with which Dr. Steindler did things. Henry H. Sherk, MD I. Orientation a. Definition As the term “osteoporosis” is commonly applied, it means a pathological condition of bone in which the essential feature is the thinning of bone trabeculae with widening of the Haversian canals and of the marrow spaces. In excentric osteoporosis bone is absorbed from the inside and the absorption gradually progresses toward the periphery, while in concentric osteoporosis the process is reversed and the absorption progresses from the periphery toward the center of the bone. Obviously, this distinction holds good only for the long bones, such as femur or tibia or metatarsals. In the short bones of wrist or ankle, which have no cortical shell covering the cancellous core, osteoporosis is entirely an endosteal deficiency. The essential feature is that the normal equilibrium between absorption and apposition of bone is overthrown. Absorption goes on at its usual rate; but apposition has become defective. b. The Significance of Osteoporosis There is nothing pathognomonic about osteoporosis. Like fibrosis of the bone marrow, it is a reaction to many underlying causes; in one case it may be due to an endocrine deficiency, in another to metabolic disorders, in a third to circulatory disturbances. It is the identification of the underlying cause which is the diagnostic problem, not the anatomical findings of the bone changes themselves. II. The Pathogenesis of Osteoporosis Table I gives some of the principal causes of osteoporosis. The following causative factors are worthy of discussion: Inactivity and immobilization Circulatory disturbances, both idiopathic and those following trauma; neurovasomotor disorders, Sudeck's atrophy Metabolic deficiencies, including avitaminosis\ Endocrine deficiencies Osteoporosis as a reaction to neighboring inflammatory conditions Senile osteoporosis Fig 1: Arthur Steindler is shown.Table I Pathogenesis Inactivity and immobilization Circulatory disturbances from vascular disease or following trauma Neurovascular disturbances Metabolic deficiencies; avitaminosis Endocrine imbalance or deficiency Osteoporosis from neighboring inflammatory conditions. a. Inactivity and Immobilization Movement stimulates osteoblastic activity; the bones of the limb immobilized in plaster or braces undergo progressive osteoporosis, which results in thinning of the trabeculae and causes loss of density in the x-ray picture (figure not shown). In the weight-bearing bones, it will be observed that the first to succumb to atrophy are the trabeculae of the secondary system; the primary, more essential ones, particularly those which sustain weight and pressure stresses, maintain themselves longer. This is shown well in the structure of the vertebral bodies. Here the persistence of the perpendicular pressure-resistant trajectories causes the peculiar striated appearance of the vertebrae. In immobilization and non-use, the factor responsible for the osteoblastic deficiency which produces the atrophy is not quite clear. Some believe it is the ischemia and the retarded metabolism, some that it is venous congestion brought about by the inactivity of the muscles (figure not shown). b. Circulatory Disturbances 1. Trauma What affects the balance between apposition and absorption of bone in traumatic events? It is commonly observed that following trauma, be it a fracture, a dislocation or even a severe sprain, decalcification occurs to a degree which cannot be accounted for by the immobilization alone. There must be a vasomotor disequilibrium at work. There is also a hypercalciuria observed in fractures, denoting an abnormal drain on the calcium reserve. Decalcification means hyperemia since avascular bone does not become rarefied. First a hyperemic rarefaction occurs at the ends of the fragments and then the local calcium from the bone becomes fixed to the newly formed connective tissue at the site of the fracture, at the provisional or periosteal callus. It is well known that the lower pH at the fracture site causes absorption mediated by the local hyperemia, at an early stage. This effect is noticeable from the start. The cortex loses its density and becomes cross-striated. 2. Vaso-Dilatory Passive Hyperemia in Neuro-Vasomotor Disturbances A similar osteoporotic effect is seen in the passive hyperemia from vaso-dilatation which occurs after sympathectomy. As a matter of fact almost any trauma, even if involving the soft tissues alone, is likely to produce a reflex hyperemia which results not only in atrophy of the neighboring bone but interferes with the circulatory exchange of the soft tissues as well. Here belongs also Sudeck's post-traumatic atrophy. A case is described of strain of the ankle joint followed five months later by osteoporosis of the bones of the foot. Usually this vasodilatory reflex following trauma lasts only nine or ten days. But there are certain cases, especially traumatism of hands, feet, digits, or carpus, in which the sympathetic vasodilatory effect persists for weeks or months, as in Sudeck's atrophy, and in which the sympathetic effect is eliminated by peripheral sympathectomy or even by ganglionectomy (figure not shown). Kümmell's kyphosis, which always has been a controversial subject, is according to Leriche the result of vasomotor disequilibrium and not really a fracture, not a mechanical event. It is an osteoporosis. Kümmell's original concept of its being an undiagnosed fracture has now been largely abandoned in favor of a resorption by molecular necrosis, but this again requires the influence of local hyperemia. The effect of these neurovasomotor disturbances can be stated briefly as edema of soft tissue with later shrinkage and loss of elasticity, atrophy and hypertonicity of the muscles, and marked osteoporosis generally most advanced near the epiphysis of the long bones. c. Metabolic Deficiencies Causing Osteoporosis Because metabolism is under endocrine control, it is somewhat difficult to discuss osteoporosis exclusively from this angle. But whatever endocrine or circulatory factor may be behind it, metabolic deficiency as such may mean a number of things: lack of proteins, of calcium, or vitamins, or any combination thereof (Table II). Table II Protein deficiency Calcium deficiency Vitamin deficiencies General cachexia 1. Calcium Deficiency and Osteoporosis The skeleton is by far the largest depository of calcium in the body, representing a reserve interposed between the calcium absorbed by ingestion and its deposition into the bony tissues. No equilibrium and harmony in tissue metabolism can be maintained without it. Pathological signs from interferences with this mechanism of absorption and utilization, appear rather insiduously. But whether the interference is due to lack of sufficient calcium intake or whether calcium adsorption is inhibited by a lack of sunlight or Vitamin D, the bone undergoes osteoporosis. This deficiency necessarily involves all tissues of the body. It affects for instance the nervous system; low calcium content in the blood causes tetany. But most striking is its effect on bone: osteoporosis, fragility, secondary fractures and deformities. The causes of this calcium deficiency in bone, which produces the osteoporosis, are three-fold: insufficient in-take, as in hunger psathyrosis or senile osteoporosis; inability to adsorb due to lack of Vitamin D, as in rickets and osteomalacia; and breakdown of the endocrine control of calcium balance, as in parathyroid disease or in thyroid or ovarian deficiency. 2. Vitamin Deficiency and Osteoporosis (a) Vitamin C This vitamin is necessary for the metabolic equilibrium of bone. Ascorbic acid deficiency leads to subperiosteal hemorrhage; in connection with this the bone rarifies excentrically, enlarging the marrow cavity. Furthermore, ascorbic acid or Vitamin C favors the synthesis of amino acids and thereby the formation of normal bone matrix. Because the amino acids constitute the protein of living tissue, protein deficiency inhibits the synthesis of osseous matrix. (b) The Important Vitamin is D It is necessary for calcium adsorption. Being fat-soluble requires fat adsorption. Therefore, it can be understood that aside from lack of ingestion there may be loss of calcium through the intestinal tract due to inadequate adsorption, a break in the triangular balance between calcium intake, Vitamin B and gastrointestinal function. In rickets and osteomalacia, the lack of Vitamin D causes inability to mineralize newly formed bone. In osteoporosis, the formation of new bone as such is impeded. (c) A combination of these factors exists in senile or cachectic osteoporosis. This type of osteoporosis is really the product of circulatory, metabolic and endocrine factors combined. Müller3 (1924), speaking of the effect of inanition on bone, emphasized that the loss of dry substance in bone may be up to fourteen per cent. If the calcium intake is low, calcium and phosphorus must be withdrawn from bone, since the calcium and phosphorus excretion remains normal. But even if calcium intake is sufficient, the protein intake is often inadequate, and even if this is adequate, adsorption may be impeded by gall bladder or pancreatic insufficiency. Another case is the patient described by Leriche2 who had gall stone icterus with choledochus drainage, and who sustained a fracture of the spine. A graft was applied. For five years it was considered consolidated. Then the fracture site became painful again and the x-ray showed decalcification. Other authors confirm that osteoporosis of the vertebrae may be caused by a gall bladder fistula. Hunger psathyrosis is closely related to senile osteoporosis. It also is based on deficiency in calcium, Vitamin D and protein intake except that circulatory difficulties, as arteriosclerosis, play no part as they do in senile osteoporosis. d. Endocrine Deficiencies and Osteoporosis (Table III) Endocrine glands control the growth and metabolic balance of bone; as the name implies the different glands have no anatomic connection among one another in the ordinary sense, but they are closely interrelated in action and their connection is humoral via the blood stream. Like the vitamins, the hormones belong to a group of catalysing ferments, but they act on living tissue; ferments in general are specific organic catalysers of protein nature whose activity is independent of life. While hormones are produced in the endocrine glands, Vitamins are not synthesized in the body but depend on outside sources for their supply. In order that hormones perform their function as regulators of metabolism, growth, and reproduction, etc., it is necessary: That they be produced in sufficient quantities, which depends on the capacity of the specific gland; That there be no retardation in the secretion, and; That the organ receiving the action of the hormones be specifically capacitated for their influence. Table III Endocrine Deficiencies The hypophysis The adrenotropic hormones of the adrenals The thyroid The gonads The parathyroids Any hormonic disequilibrium either in itself or in connection with other factors such as vitamin deficiency, immobilization, or circulatory stasis, may be the background of osteoporosis. It remains only to identify the specific gland to which the effect is to be assigned, which is somewhat difficult because of the functional inter-relationship of these glands (S. Schnitman4). (1) The hypophysis stimulates the growth of bone and cartilage as well as having a trophic effect on all other endocrine glands. Its deficiency causes intense rarefaction of bone. There is an hypophyseal osteoporosis which is caused by a basophilic adenoma. Excess of the adrenotropic hormone of the hypophysis has a depressing effect on osteogenesis, while insufficiency of the gland inhibits the normal utilization of ascorbic acid so necessary for periosteal and endosteal growth. (2) The principal anabolic hormones which stimulate and facilitate osteoblastic activity are, besides the thyroid, the androgenic and estrogenic hormones of the gonads. Their insufficiency leads to osteoporosis. Here belongs menopausal osteoporosis (figure not shown), which is caused by a marked lack in the excretion of estradiol. We see this type of osteoporosis in women with artificially produced menopause. When the menopause occurs slowly, estrogen production does not stop suddenly and it may take twenty years to develop osteoporosis. (a) The estrogen: this hormone reduces calcium and phosphorus excretion. After castration many women complain of pain in the flank, or pelvis; the most persistent symptom is backache accompanied often by vertebral collapse, a dorsal kyphosis occurring under the effect of osteoporosis; some patients even become bed fast. The mineral loss of the skeleton may be as high as fifty per cent. The spine shows the well known biconcavity of the vertebral bodies and Schmorl's nodes penetrating into the cancellous bone. (b) The androgen: its effect is similar to that of the estrogen; its deficiency is slower in producing calcium loss but the effect seems to last longer. Most effective are combined deficiencies of both gonadal hormones. (3) The thyroid hormone acts pre-eminently during the evolution of the individual, particularly upon the maturation of tissues in general. It stimulates growth, affecting mostly the enchondral osteogenesis. Hypothyroidism increases bone density. Hyperthyroidism produces osteoporosis by impeding the normal formation of osteoid substance and by inhibiting endosteal ossification (figure not shown). (4) The parathyroid glands have the most marked immediate effect on the calcium balance. Removal of all parathyroid gland tissue in the animal causes a rapid fall of blood calcium. Tetany develops. Intravenous injection of the parathyroid hormone restores the blood calcium level; continued injection causes absorption of calcium from the skeleton; the blood level becomes high and the calcium is excreted by the kidneys, producing kidney stones. The four parathyroid glands maintain normally a very sensitive regulation, secreting only the amount necessary to maintain the blood calcium at normal level. But if the parathyroid activity is increased by hypertrophy of the glands or by an adenoma, the result is a general decalcification of the skeleton and a high blood calcium level (Erdheim1). This condition obtains in the generalized fibrocystic disease of von Recklinghausen or osteitis fibrosa cystica generalisata. This fibrous dysplasia of the bone manifests itself by generalized pain, weakness, tenderness of the skeleton, fractures and deformities, and the x-ray shows a generalized osteoporosis. At the same time, the urinary output of calcium may be so increased that the blood calcium level remains normal in spite of the calcium loss of the skeleton. Consequently, both blood and urinary calcium must be measured to appreciate the rate of loss of calcium from the skeleton. From the therapeutic standpoint, it is important that the equilibrium produced by removal of the hyperactive gland is very labile; hypocalcemia follows, which again must be taken care of by the administration of parathormone. III. Clinical Pathology (Table IV) a. Immobilization Osteoporosis Immobilization atrophy affects mostly the metaphysis of the long bones and the small bones of the hands and feet. Table IV Anatomical and Clinical Pathology The immobilization osteoporosis Radiation osteoporosis. X-rays, ultrasonic waves. Metabolic deficiency osteoporosis The endocrine deficiency osteoporosis The senile and cachectic osteoporosis In plaster fixation with recumbency, the calcium output increases for four to five weeks and then reaches a constant level. There is also a loss of nitrogen and protein, beginning at the fifth to sixth day and attaining its peak at the end of the second week. These changes produce a negative calcium balance with hypercalciuria. The essential feature is that there is no uncalcified or decalcified bone but only the osteoclastic rare-faction without compensatory apposition of new bone. As an example of inactivity osteoporosis Policard and Leriche cite the diffuse osteoporosis which follows traumatization of a peripheral nerve. Immobilization by section of the tendo Achillis, done experimentally, produces atrophy of bone even if function is only partially eliminated. Similar findings were those of Allison and Brooks after either plaster immobilization or section of the nerve plexus in dogs. After section of the sciatic nerve, most observers report thinning atrophy but no loss in length growth. Premature fusion is observed after the long-continued immobilization of growing bone, as for instance in tuberculosis of the hip joint. The x-ray changes are as follows (Sisson5). In the early stages, there is a marked juxtaarticular rarefaction corresponding to the microscopic picture of osteoclastic absorption. Later the osteoporosis becomes more generalized and cyst-like areas of cavitation appear. In the astragalus such cysts can be seen in head and body; similar ones occur in the os calcis. When the epiphyseal plate becomes involved in the osteoporotic process, a gap appears in the plate letting the bone trabeculae pass from shaft to epiphysis, which ultimately leads to premature fusion. These changes are at first reversible, and under proper treatment repair sets in with the formation of a slender network of newly developed bone trabeculae. In growing bone, the epiphyseal cartilage is particularly susceptible to immobilization; cartilage cells atrophy and finally succumb, growth is arrested and premature fusion appears. b. Radiation Osteoporosis This type of osteoporosis (figure not shown) is the effect of damage to the osteoblasts. Small doses affect the osteoblasts only temporarily and regeneration occurs; larger doses cause permanent changes. Fractures occur, principally of the neck of the femur after radiation for pelvic carcinoma; often the distinction must be made between osteoporotic radiation fracture and carcinomatous metastasis in the neck of the femur. We have seen bilateral fractures of the neck of the femur caused by radiation. It is important for the diagnosis that the fracture may not be displaced, showing only a fine fracture line. The patient complains of pain but is still able to walk around with a limp. The pain gradually increases and a completely displaced fracture appears (Irving Stein,6Fig. 10). Ultrasonic rays have a similar effect on bones. This is not surprising when one considers the tremendous energy and the considerable amount of heat and hyperemia which these rays produce. The main reason for their destructive effect is the so-called cavitations formed by the marked potential difference between the crest and the floor of the sound waves. The osteoporosis so produced resembles that seen in caisson disease. c. Traumatic Osteoporosis Here is a combination of several factors: reflex hyperemia, inactivity and immobilization, and in severe degrees as in Sudeck's atrophy, sympathetic nerve irritation (figure not shown). The atrophy becomes rapid and extensive; trophic disturbances appear in the soft tissues; circulatory and peripheral nerve damage is manifested by edema, infiltration and markedly increased sensitivity. There seems to be no strict dividing line, except in degree, between simple post-traumatic osteoporosis with swelling and tenderness of the soft tissues and the extreme degree of atrophy one sees in Sudeck's type. It is difficult to decide to what extent any one of these factors participates in producing the clinical picture. At any rate the osteoporosis develops more or less rapidly and appears to be more of circulatory and nervous nature than due to lack of muscular stimulus. When one considers the rapid muscle atrophy which, for instance, follows traumatic conditions of the knee, or some cases of Colles' fracture, it is difficult to eliminate nervous reflex action. Acute traumatic osteoporosis is associated with hypercalcemia; the more intense, the more extensive the trauma. d. Osteoporosis from Metabolic Deficiencies Protein lack is one of the causes of osteoporosis. The protein deficiency may be caused by hepatic or pancreatic deficiency or gastrointestinal failure. There are a low concentration of serum albumin and often a reversal of the albumin-globulin ratio. The deficiency in calcium adsorption may cause rachitis in the young or osteomalacia in the adult, but not all calcium deficiency results in osteoid bone formation. Simple osteoporosis may result. Stoelzner's report7 on so-called pseudorhachitis represents an early recognition that calcium insufficiency may produce pure osteoporosis without formation of osteoid bone. In a sense osteopsathyrosis is a form of osteoporosis; however, it is the apposition of new periosteal bone which is defective, so that the bone becomes thin and fragile and fractures easily (figure not shown). e. Osteoporosis from Endocrine Deficiencies It seems somewhat inconsistent to mention endocrine factors in juxtaposition to the metabolic factors responsible for the normal calcium balance, because the endocrines are the prime regulators of the metabolic equilibrium of the electrolytes. But they do more than that. The suprarenal hormones under the influence of the pituitary favor the reabsorption of sodium and diminish the reabsorption of potassium. Their deficiency causes sodium retention and lack of potassium. The androgens favor a positive nitrogen balance. The parathyroids regulate the calcium retention in bone and the calcium content of the blood and urine. Hyperparathyroidism produces a washing-out of calcium from bone and an overloading of blood and urine. Important for the diagnosis of hyperfunction of this gland is loss of phosphorus in the blood while the calcium concentration is high in blood and urine. In the presence of hyper-calciuria many bone conditions may be found: myeloma, metastatic carcinoma, Paget's disease or simple osteoporosis. Here one must decide whether the hyperparathyroidism is secondary to any of the above conditions and compensatory to the osteopathy, or whether it is due to a chronic renal insufficiency, or whether it is primarily due to a tumor or hypertrophy of the parathyroids as in von Recklinghausen's disease. f. General Cachectic and Senile Osteoporosis All pathogenic factors play their part: metabolic and circulatory as well as endocrine. One must look for circulatory disturbances including venous stasis, thrombosis and arteriosclerosis in all older individuals with osteoporosis. There are commonly a low nutritional level, protein and mineral deficiency and a lack of vitamins. But the one factor often overlooked is the deficiency of the endocrine glands. Parathyroid deficiency is rarely the cause of osteoporosis in the aged; more often lack of function of the gonads is responsible. The 17-ketosteroids which express the androgenic function in the adrenal cortex and testicle gradually decrease with age. The difficulty lies in distinguishing the physiological osteoporosis of the aging from the pathological. There are many cases in which excessive atrophy is found in individuals of the fifth or sixth decade. The changes are, therefore, more quantitative than qualitative and are the expression of a general senility, often premature, which includes circulatory and alimentary as well as endocrine factors. Most marked are the symptoms in spinal osteoporosis. When pain appears, it is usually in the lumbar region first. Involvement of the upper dorsal spine causes radiation in shoulder and arm, that of the lower into the territory of the lumbosacral plexus. But radiation around the thorax from pressure on the intercostal nerves is by no means rare. The x-ray shows the characteristic fish-tail vertebrae; spontaneous compression fractures of the osteoporotic vertebral bodies are most common. As collapse of the vertebrae becomes fixed, rigidity sets in and kyphosis develops. It is this process of gradual fixation which is painful and requires treatment. A differential point against hyperthyroidism is the continuous hypercalciuria in the latter condition. Senile osteoporosis has a predilection for the spinal column and the pelvis (figures not shown). The extremities are less involved. IV. Treatment (Table V) The treatment for immobilization osteoporosis is to minimize bed rest, to exercise the muscles of the body and to institute function as soon as possible. This may be considered as the general background. However, according to the nature and type of osteoporosis and the age and condition of the patient, many additions and alterations of the treatment plan must be made. For instance in traumatic conditions, severe sprains or fractures, timely procainization of contusions and adjustment of fractures and proper immobilization in both instances may prevent subsequent posttraumatic osteoporosis. Secondly, the general condition, especially in the aged, requires special supportive treatment such as high doses of Vitamin B12, ascorbic acid combined with sun light, ultraviolet light, and physical therapy. Table V Treatment General and supportive Local treatment of surgical traumatism Specific treatment of metabolic deficiency Treatment of endocrine imbalance The problem of senile osteoporosis A special well-balanced diet, commensurate with the patient's age and constitution, must be given. We prefer a diet high in protein, much less in carbohydrates and least in fat, considering the restricted activity and the diminished ability of the gastrointestinal tract to absorb fat. And thirdly, special attention should be paid to endocrine requirements. Sometimes various hormones must be used. Senile osteoporosis especially should be treated from the endocrine and nutritional point of view. Specifically, for osteoporosis of the menopause, use testosterone with estrogen; the same for the osteoporosis found in rudimentary development of the ovaries usually accompanied by other congenital deformities; twenty-five mg. of testosterone daily in combination with 1.25 mg. of estrogen by mouth three times a day are recommended by Irving Stein.6 The senile osteoporosis which is the result of endocrine, nutritional, metabolic, and circulatory factors must be treated accordingly, i.e., by supportive, nutritional and hormonal treatment, and here again we prefer the combination of androgen and estrogen. Androgen particularly favors fixation of the protein and the formation of a good quality of osteoid matrix. It is, therefore, useful in all types of generalized osteoporosis. The ingestion of calcium and of Vitamin D is not in itself sufficient to stimulate osteoblastic activity in osteoporotic patients. For the localized osteoporosis caused by circulatory and vasomotor disturbances such as Sudeck's atrophy, Leriche introduced periaterial sympathectomy; however, this has been largely abandoned in favor of procainization of the sympathetic trunk or ganglionectomy. Finally, one must not overlook the frequent hyperemic decalcifications which occur in the spine, especially the cervical vertebrae in the wake of neighboring inflammatory conditions. Furthermore, torticollis and subluxations due to non-inflammatory, circulatory osteoporosis and ligamentous relaxation have been reported. Most of these local osteoporoses are reversible and depend upon the treatment of the local condition which is beside the scope of this presentation.