Different patterns of extension and recurrence in algodystrophy.

A true recurrence at exactly the same site is quite unusual in algodystrophy. Local or regional extension is possible. The bone scan is an easy way to demonstrate that the areas successively affected are not the same. An apparent local recurrence could in fact be a microscopic compression fracture of trabecular bone or cortical fractures or part of a factitious disorder.

Further vascular, bone and autonomic investigations in algodystrophy.

Direct clinical observation is the most common means of diagnosing algodystrophy. Further investigations may be helpful to rule out other pathological conditions, such as occult or stress fractures or avascular osteonecrosis and to obtain a better understanding of algodystrophy. Transient vascular hyperpermeability in the affected part is well demonstrated by the clinical findings, the MRI signs, and the three-bone scan features. 99m Technectium EHDP bone scan provides an evaluation of the vascular abnormalities and of the osteoblastic activity. Dermal microcirculation and its reactions to sympathetic stimuli are investigated by laser doppler fluximetry and videophotometric capillaroscopy. Perhaps the sweat test does unveil what might be specific about algodystrophy. The amount of bone loss in algodystrophy in a few weeks or months is what might be expected over 10 years during the natural history of uncomplicated osteoporosis. An initial fracture is undoubtedly an initiating event in the appearance of algodystrophy, but patients suffering from algodystrophy may still have significant osteoporosis for a long period and hence be at risk for fracture. Densitometry could be an aid to the diagnosis and probably to monitoring treatment as well. The local colonization of fibroblasts following the transient stage of hyperpermeability must be kept in mind to explain the results of joint, bone, muscles or neurological investigations in late algodystrophy.

Polyostotic Paget's disease. A search for lesions of different durations and for new lesions.

We conducted a medical record-based study of 169 patients with polyostotic involvement identified among 200 Paget's disease patients. Follow-up was 15 to 41 years in 31 cases. The pelvis was the only bone that was more likely than not to be involved bilaterally. All the other paired bones were more likely to be involved unilaterally and when both sides were involved the two lesions were very often frankly asymmetric. In a given patient, the duration of the various pagetic lesions, estimated from their size and from data provided by an earlier study on the rate of progression of pagetic lesions, was similar in some cases and showed marked differences in others. Aggregation of the lesions into two or three disease duration groups was seen in some patients, suggesting that Paget's disease may occur in two or three waves. When we reviewed the radiographs from 30 patients with a mean follow-up of 23 years, we found new lesions in ten patients. However, a review of bone scans from 18 patients with a mean follow-up of 11 years failed to uncover any firm evidence of new lesion development, perhaps because all these patients received bisphosphonate therapy (etidronate, tiludronate, pamidronate). We also found data suggesting that the disease process spread across a joint in some patients, even in the absence of degenerative joint disease. In particular, in several cases an extensive pagetic lesion was seen on one side of a joint and a considerably smaller lesion on the other side.

Progression in length and width of pagetic lesions, and estimation of age at disease onset.

The mean annual rate of increase in the length of pagetic lesions was 8.5 mm for the skull and tibia and 9.4 mm for the femur, after a follow-up of nine to 16 years according to the bone. The fastest rate of progression was seen at the femur and was 24 mm per year. Thirty years were required for lesions to spread to the entire pelvis and 13 years to all the bones surrounding the obturator foramen. Saber shin deformity of the tibia without involvement of the distal fourth of the bone indicated a disease duration of 25 years, as did involvement of the entire skull. The annual rate of increase in the width of lesions varied widely across patients and was not influenced by gender. Thickening of the skull occurred at a rate of about 4 to 5 mm per decade after pagetization of the bone, although faster rates were seen in some patients; a sandwich-like appearance with a thickness exceeding 32 mm was seen in six of the 29 skulls studied. At the femur and tibia, the increase in width was 10% to 30% per decade after pagetization of the bone; faster thickening was seen in some tibias with saber shin deformity. The thickness of the ischial tuberosity increased by 3 to 4 mm per decade after pagetization. Determination of the degree of hypertrophy is useful for estimating the duration of pagetic lesions when the entire bone is involved at first presentation. Involvement of the entire pelvis indicates a disease duration of 30 to 40 years according to whether the bone is hypertrophied or not. An estimation of age at disease onset in 70 patients suggested that the first bone lesions probably appeared before the age of 30 years in 45 patients (64%), whereas the diagnosis was established before 30 years in only three patients. These data suggest that Paget's disease may be a disease of teenagers and young adults.

The initial site of bone lesions in Paget's disease. A review of two hundred cases.

We retrospectively evaluated the initial site of bone lesions in 200 patients with Paget's disease. There were 117 males and 83 females. Mean follow-up was 13 years in 98 patients. The initial site can be determined accurately only if less than one third of the bone is involved. Paget's disease usually begins in the cancellous bone of an epiphysis or metaphysis. A diaphysis is the first site involved in some instances, and the anterior subperiosteal area of the proximal half of the tibia in a very small number of cases. The distribution of initial pagetic lesions in our series is reported for each of the main bones. Lesions usually arose in the proximal ends of long bones, which are richly vascularized but contain no hematopoietic marrow in adults. This suggests that the distribution of pagetic lesions may be more closely dependent on local circulatory conditions than on the presence of hematopoietic marrow, which is, however, the only source of osteoclasts.

An etiologic study of Paget's disease.

The objective of this case-control questionnaire study was to determine whether a history of measles or of dog ownership occurred with different frequencies in Paget's disease patients and in age- and sex-matched controls. Clustering of Paget's disease cases in geographic foci was also looked for, as well as a difference in the prevalence of Paget's disease according to whether the subsoil was composed of rocks from the primary or the tertiary-quaternary geologic periods. Completed questionnaires were obtained from 247 Paget's disease patients and 281 controls. Paget's disease was significantly associated with a history of measles (odds ratio, 2.46) but not with a history of mumps (odds ratio, 0.79) or with dog ownership (odds ratio, 0.97). The 174 cases of Paget's disease in subjects from the study district were distributed throughout the district, with no geographic clustering. This result was confirmed by the analysis of the ratios of Paget's disease cases over the total population in each county in the study district. The incidence of Paget's disease was slightly higher in areas with a primary subsoil, but the difference was not statistically significant (chi-square, 0.79; P = 0.37).

Current prevalence of Paget's disease of bone in a region of France (Anjou).

To study the prevalence of Paget's disease in a region of France (Anjou) we conducted a two-part study. 1) One hundred randomly selected medical records of Paget's disease patients managed in a rheumatology department were studied to determine the rates of occurrence of pagetic lesions at each skeletal site. Availability of a radionuclide bone scan done before treatment initiation and of radiographs of hyperactive areas was required for inclusion into the study. In 91% of patients, pagetic lesions were visible on the lumbar spine-pelvis-femoral head film. 2) We looked for pagetic lesions on intravenous urograms done in 600 urology department patients (to minimize recruitment bias). The 307 males and 293 females had a mean age of 65.4 +/- 8.7 years (range 50-91). Films classified by the evaluator as showing definite or doubtful pagetic lesions were read by five other evaluators in a blind manner. Among the 11 patients (seven males and four females) found to have Paget's disease, only one was younger than 65 years. Prevalence was higher in males (2.50 +/- 0.79% than in females (1.50 +/- 0.5%). These prevalences are lower than those reported in the United Kingdom.

A new anatomic index based on current knowledge for calculating the cumulative percentage of pagetic bone per subject and other parameters.

New data provided by dual-energy X-ray absorptiometry, together with discordances between Howarth's and Coutris' tables for estimating the percentage of bone tissue affected with Paget's disease in a given individual, prompted us to reevaluate the percentage of bone tissue contained in each segment of the skeleton. We weighed each bone in the skeleton of a 30-year-old male, calculated weight ratios from a collection of 48 bones, performed dual-energy X-ray absorptiometry measurements in 22 patients using a Hologic QDR 2000 apparatus, and obtained information from a company that supplies medical schools with human skeletons. We used these data to develop a new anatomic index. The percentage of bone tissue in the skull was 17 in males and 21 in females versus only 11 in Howarth's table; differences were also found at other sites, including the spine (8.5% versus 11%), the femur (9.5% versus 8%), the sacrum (2% versus 3%), and the ribs (5% versus 9%). Our index is useful for calculating the percentage of pagetized bone (i.e., bone in which pagetic lesions develop during follow-up) but underestimates the total percentage of pagetic bone because of the increase in bone mass associated with Paget's disease.

[Osteomyelitis in the pagetic tibia]. / Ostéomyélite sur tibia pagétique.

Osteomyelitis developing in pagetic bone is a very rare event, of which only one instance has been reported to date, in a patient with mandibular disease. We have managed three patients with osteomyelitis of a pagetic tibia. The portal of entry was a skin lesion in all three cases. A Gram-negative organism was found in all three cases and was associated with the anaerobe Bacteroides melaninogenicus in one case. One of the patients was lost to follow up before eradication of the infection. Amputation was required in the other two after unsuccessful antimicrobial therapy for 23 and four years, respectively.

Efficacy and tolerability of a new formulation of oral tiludronate (tablet) in the treatment of Paget's disease of bone.

We sought to assess efficacy and safety of a new oral formulation (tablet) of tiludronate in Paget's disease of bone. We studied 128 patients with Paget's disease in an open-label uncontrolled trial. Patients received a daily dose of 400 mg oral tiludronate (two tablets). Treatment was for 6 months. Serum alkaline phosphatase activity (SAP) and fasting urinary excretion of hydroxyproline/creatine (OH/Cr) were measured every 3 months, as were biochemical parameters reflecting renal, hepatic, and hematologic functions. Analgesic efficacy was self-evaluated from a visual analog scale (VAS). Statistical analysis revealed a significant reduction from baseline in SAP and OH/Cr levels, as well as VAS scores. In the whole population with evaluation under treatment, there was a reduction in initial SAP activity after 3 months (47.2 +/- 2.2%, mean +/- SEM) and 6 months (58.3 +/- 2.3%). In the population with SAP levels above twice the upper limit at inclusion and with evaluation at month 3 and month 6 (n = 96), the reduction in SAP levels was 49.3 +/- 2.4% after 3 months and of 59.5 +/- 2.6% after 6 months (ANOVA time effect, p = 0.0001). Aside from mild gastrointestinal disturbances, as experienced with other oral bisphosphonates, clinical tolerance was good. Exhaustive biochemical investigation failed to reveal significant toxicity of tiludronate tablets at the dose of 400 mg/day. The dose of 400 mg daily of this new formulation appears to be a satisfactory tiludronate regimen for the treatment of Paget's disease of bone.

[Transient painful lumbar blocks]. / Les à-coups douloureux bloquants lombaires.

Recurrent painful locking of the lower back is suggested as an appropriate term for designating sudden episodes of jabbing low back pain with locking of the spine occurring in the absence of unusual exertion, resolving within one or two minutes, and recurring many times over several weeks or months. This retrospective study included 20 outpatients classified as having recurrent painful locking of the lower back between 1978 and 1992. Inclusion criteria were availability of roentgenograms taken at the time of the acute symptoms and a follow-up of at least two years. Two typical cases are reported with diagrams to show the timing of recurrent painful locking of the lower back with respects to other low back symptoms. Mean age at onset was 56 years. Seventy per cent of patients were females. A 10-year to 30 year history of lumbago was found in every case. Recurrent painful locking of the lower back occurred substantially later than lumbago suggesting that it denoted more advanced damage to the lumbar spine. Pathophysiologic hypotheses are discussed: the causative lesion may be a mobile flap at the posterior aspect of the anulus. In most patients, the symptoms resolved within six months.

[Migratory algodystrophy of the lower limbs involving the foot and complicated by two fatigue fractures. An histological bone study]. / Algodystrophies itératives des membres inférieurs, migratrices sur les pieds, compliquées de deux fractures de fatigue. Etude histologique osseuse.

A 62 year old male developed transient osteoporosis algodystrophy successively in several sites of the lower limbs (8 episodes of involvement of one or two sites over an 8-year period) three years after surgery for a chromophobic pituitary adenoma. Two stress fractures developed, during the sixth and seventh years, respectively, in bones previously affected by osteoporosis. A biopsy specimen from the distal tibia showed thin bone trabeculae and reduced cellular activity. The only etiologic factor was the patient's psychological profile characterized by anxiety and introversion.

[Lower back pain in physicians. Epidemiological aspect and risk factors]. / Les douleurs rachidiennes basses chez les médecins. Aspect épidémiologique et facteurs de risque.

The purpose of this study was to evaluate as accurately as possible, in a well-defined population subgroup, the prevalence and incidence of lower back pain, the impact of this symptom on professional activities and personal life, and the influence of risk factors. Members of the medical profession were considered particularly apt to accurately and reliably report their personal experience with lower back pain and were therefore selected for this survey. Five hundred 93-item questionnaires were sent to a representative sample of physicians in the Maine-et-Loire district, France. Response rate was 93%. Prevalence of lower back pain at the time of the survey was 32% and cumulative prevalence was 62%. Static spinal disorders (exaggerated lordosis, scoliosis, unequal length of lower limbs) and injury to the spine were found to be risk factors. Occupation-related stresses to the spine reported as being responsible for lower back pain included bending forward for prolonged periods, lifting weights, driving, and prolonged sitting.

[Anti-centromere antibodies. Study of 67 positive sera]. / Anticorps anti-centromères. Etude de 67 sérums positifs.

From a series of 67 sera containing anticentromere antibodies we endeavoured to determine the principal clinical or biological peculiarities of these antibodies. The titers of anticentromere antibodies were usually high, with few differences between patients. Humoral immunity was frequently perturbed, with antinuclear autoantibodies (without anti-Scl 70), anti-mitochondria antibodies, rheumatoid factors, circulating immune complexes, etc. The disease predominated in women (97%) whose age and duration of symptoms varied considerably. The most frequent clinical manifestation noted in the 47 reports analyzed was Raynaud's phenomenon (93%) which in most cases (90%) was part of a complete or incomplete CREST syndrome. Telangiectasias, calcinosis and acrosclerosis were the main witnesses to the duration of these sclerodermas. Our findings were concordant with those of previous studies. However, the frequency of sicca syndrome (76%) was unexpected, and must be related to 2 laboratory results: the quasi-absence of anti-SSA and anti-SSB antibodies in our patients and the presence of two monoclonal immunoglobulins (IgM kappa and IgG lambda). There may be some degree of independence between the sicca syndrome and the sclerodermal manifestations.

[Investigation of phosphorus calcium metabolism after oral phosphorus supplementation]. / Exploration du métabolisme phosphocalcique après supplémentation orale en phosphore.

Effects of oral administration of phosphorus on phosphorus and calcium parameters and on bone metabolism hormones were investigated in two studies: in the first, 12 young female adults and 8 females over 50 years of age took a single oral load dose of 780 mg elemental phosphorus, whereas in the second study assays were performed 5 and 15 days after initiation of twice-daily phosphorus supplements in 19 young adults, 14 subjects above 50 years of age who were free of osteoporosis, and 12 patients with osteoporosis also over 50 years of age. The phosphorus load was associated with an increase in intact parathyroid hormone levels (iPTH 1-84), which was more marked in subjects above 50 years of age than in younger adults. On the 15th day of phosphorus supplementation, there was no significant increase in baseline iPTH and no change in baseline dihydroxyvitamin D or osteocalcin levels; during the Nordin tests, the fractional calcium excretion index (CaU/CrU) and the fractional hydroxyproline excretion index (OH Pro/CrU) remained unchanged. In contrast, the phosphorus load was followed by a decrease in the maximum phosphorus reabsorption threshold (TMP/DFG), which was more marked on the 5th day than on the 15th day; a slight fall in serum phosphorus levels was also seen on the 15th day. These findings suggest that phosphorus supplementation should be intermittent rather than continuous. Analysis of subjects aged 50 to 69 years failed to disclose any significant differences between patients with and without osteoporosis.

Ankylosing spondylitis and monoclonal gammopathies.

From 1960 to 1990, 557 patients with ankylosing spondylitis (428 men, 129 women) were diagnosed and indexed in the department of rheumatology. Monoclonal gammopathies were found in seven (five men, two women) patients (1.3%). With one exception, ankylosing spondylitis preceded monoclonal gammopathies by many years. The distribution of the isotypes of the mIg found in these seven patients was striking when compared either with previous reports of an association between ankylosing spondylitis and monoclonal gammopathies or with local data on the epidemiology of monoclonal gammopathies: five patients with IgG, four of them of the lambda (lambda) type, and two IgM, both of the kappa (kappa) type were found; no patients with mIgA were recorded. Two patients were HLA-B27 positive and had slight and transient monoclonal gammopathies, whereas three subjects were HLA-B27 negative and had important spikes, corresponding in two subjects to malignant diseases. This observation raises the question of whether the coexistence of HLA-B27 and ankylosing spondylitis might provide a protective action. Epidemiological studies are required to clarify such points.