D. Kuntz

Bone mass in middle-aged osteoporotic men and their relatives : Familial effect

Severe idiopathic osteoporosis in middle‐aged men is still poorly understood. The aim of this study was to assess the contribution of genetic factors in these patients. We studied 38 men (mean age ± SD, 50 ± 11 years) presenting with vertebral or peripheral bone fractures due to primary osteoporosis and 73 of their relatives divided into four subgroups: 19 brothers, 22 sisters, 13 sons, and 19 daughters. The control group comprised 199 age‐matched subjects. In all subjects, we measured bone mineral density (BMD) and calculated the Z score at the lumbar spine (LS) and femoral neck (FN) based on the fitted BMD value in the controls. LS BMD values were lower in each of the four subgroups compared with the age‐matched controls. The mean Z score for the overall group of 73 relatives was decreased compared with the age‐matched controls (−1.28 ± 1.48 at the LS and −1.03 ± 1.19 at the FN) and was not influenced by gender or by whether the relatives were siblings or children. An LS Z score < −1) was found in 54.8% of the relatives of osteoporotic patients versus 17.4% of the control subjects (risk ratio, 3.2). Alcohol and tobacco abuse are well‐known risk factors for osteoporosis in men. Among the 38 osteoporotic patients, 7 were heavy smokers (>20 pack‐years), 8 were both heavy smokers and drinkers (>80 g/day for at least 10 years and γGT > 40 UI/l), and 23 had neither of these risk factors. BMD, Z score, and anthropometric data were the same in patients with and without risk factors. Decreases in LS and FN Z scores were similar in relatives of patients with and without risk factors. In conclusion, low BMD is observed in relatives of osteoporotic men with or without risk factors for osteoporosis, indicating that familial factors contribute to primary osteoporosis in middle‐aged men.

Bone histomorphometric reproducibility in normal patients

SummaryTo study bone histomorphometry reproducibility in normal subjects, we performed during orthopedic surgery bone biopsies in 16 post-menopausal women. Each woman had four bone biopsies, two at the usual site in the iliac crest, one on the left and one on the right side, and two other biopsies just behind the usual site, one at each side. We performed measurements of trabecular bone volume, relative osteoid volume, osteoid surfaces, osteoclastic resorption surfaces and calcification front. The average values of the 16 patients were compared, on the one hand, two by two, by a student test, and on the other hand, by a variance analysis. By these two methods the results showed no significant difference between the average values of the 16 patients at each location for any of the histomorphometric parameters studied. However, there was a location variation which was estimated by the intra-individual variation for a given patient. On the other hand, we calculated from the variance analysis the location variance for a group of 10 to 100 patients. In any case all the parameters had a location variation which was high for osteoclastic resorption surfaces and relative osteoid volume when expressed in % of the absolute value of these parameters. The variation of the trabecular bone volume was 0–46. 15% (95% confident limit interval) in a single patient and the hypothetical value of the location variation was 41.6% for a group of 10 patients and 13.0% for a group of 100 patients.

Bone histomorphometry in hemod alysed patients

Abstract We performed bone histomorphometry in thirty hemodialysed patients. Ten patients had a double iliac bone biopsy to estimate bone histomorphometry reproductibility. There was no difference between the mean results for each of the 10 patients at each site. However, there was an intra-individual variation which was small for the parameters of formation and particularly osteoid thickness and mineralizing rate and greater for resorption parameters. Mineralization rate appeared the most reliable and discriminant parameter. These 30 patients were separated in two groups according to their mineralizing rate (MR); patients with an MR > 0.3 μ/day were in group I and had severe hyperparathyroidism without major impairment of bone mineralization and high formation rate. They also had high serum alkaline phosphatases and high serum parathyroid levels measured with a COON terminal antibody (iPTH). Patients with a low MR

Decreased bone formation in osteoporotic patients compared with age-matched controls

SummaryIn order to study trabecular bone remodeling in postmenopausal osteoporosis we compared bone biopsies of 44 osteoporotic women aged 50–70 to those of 23 nonosteoporotic women, matched for age, who had a bone biopsy during anesthesia for knee arthritis. Trabecular bone volume, mean wall thickness, osteoblastic surfaces, labeled surfaces, and bone formation rate were decreased in osteoporotic women compared with control women. The osteoclast number and the osteoclastic surfaces were the same in the two groups. The normal distribution of the histomorphometric static parameters in osteoporotic patients did not allow the separation of subgroups. These data indicate that decreased bone formations is a major contributing factor leading to trabecular bone loss in postmenopausal osteoporosis.

Bone histological heterogeneity in postmenopausal osteoporosis: A sequential histomorphometric study

We studied sequential bone biopsies performed at 6 to 24 month intervals from 14 untreated osteoporotic women (64 +/- 7). Subgroups were defined, respectively, by increased osteoclastic resorption surfaces and decreased osteoblastic surfaces +/- 2 S.D. Normal values were obtained from bone biopsy of 23 normal women (61 +/- 8). When patients were divided into subgroups according to the above criteria the first biopsy showed that 3 out of the 14 patients had high resorption surfaces and 6 had low osteoblastic surfaces. Eight patients spontaneously changed during the study. In 2 patients there was a change in resorption surfaces, in 3 in osteoblastic surfaces and in 3 a change in both osteoblastic and resorption surfaces was observed. Considering the first or second bone biopsy results the patient variance was higher than the control subjects variance; however the variance between the first and second bone biopsy of one patient was not different from the variance inside the group of patients. The average intraindividual variation of the parameters on sequential biopsies was of the same order as the one we previously observed on simultaneous bone biopsies of normal and hemodialyzed patients. We concluded that if osteoporosis is a heterogeneous disorder, subgroups cannot be definitively defined on the basis of cellular parameters of bone remodelling assessed on bone biopsies.

Nonosteomalacic osteopathy associated with chronic hypophosphatemia

SummaryWe studied bone histomorphometry in 19 patients with chronic hypophosphatemia related to an idiopathic renal phosphate wasting and without histological osteomalacia. Nine patients had renal lithiasis (group 1), three had radiological osteoporosis (group 2), and seven had lumbar pain (group 3). In the whole group of 19 patients, serum phosphate levels were low (24.9±2.1 mg/l), calcium in blood was normal, calcium in urine was increased, and iPTH was low. Histomorphometric data showed decreased osteoblastic surfaces with normal resorption surfaces, normal osteoid volume and calcification front. There was no correlation between serum phosphate level and histomorphometric parameters. There was no statistical difference between the data of the 3 groups of hypophosphatemic patients. We concluded that chronic hypophosphatemia in the adult doses not always lead to osteomalacia but to an unusual osteopathy characterized by an osteopenia due to an isolated decrease in bone formation. The respective importance of phosphate deficiency and of decreased iPTH level in the pathogenesis of this osteopathy is uncertain.

Cytokine Release from Marrow Mononuclear Cells is Negatively Correlated to Cortical Elasticity in Non-Osteoporotic Postmenopausal Women

Abstract. Activation of bone remodeling is likely to be under the control of mechanical factors acting, in part, through soluble local factors. We therefore investigated a relationship between cytokine production by marrow cells and bone elasticity. We studied 36 non-osteoporotic postmenopausal women undergoing hip arthroplasty for hip arthrosis (mean age: 68 ± 8 years; lumbar BMD Z-score: +0.54 ± 0.33 SD). Adherent marrow mononuclear cells were cultured for 48 hours with autologous plasma, and supernatants were harvested for PGE2, IL-1, TNF-α, and IL-6 measurements. Femoral neck cortical bones were removed during surgery for cortical histomorphometric evaluation and determination of elasticity indices (C33) using ultrasonic transmission method. In this nonosteoporotic population, femoral neck longitudinal elasticity indices were inversely correlated to both cortical thickness (r=−0.58, P < 0.01) and cortical porosity (r=−0.33, P < 0.01). The longitudinal elasticity indices were also negatively correlated to basal IL-1 and TNF-α release by adherent mononuclear marrow cells (r=−0.59, P < 0.01; r=−0.60, P < 0.01, respectively). However, no relationship was found between the three cytokines tested and either cortical thickness or porosity. These data show a link between cortical biomechanical properties and local factors involved in bone remodeling. We suggest that increased bone elasticity decreases transmission of strain, which in turn decreases cytokine release from marrow cells. However, whether cytokines influence bone elasticity or vice versa remains to be demonstrated.

Biopsie médullaire et critères diagnostiques des mastocytoses systémiques : 9 observations

Systemic mastocytosis is a rare disease involving chiefly the bone marrow and causing diagnostic problems. The authors report 9 cases confirmed by bone marrow biopsy. This study provides a reproducible method of mast cell (MC) count and shows that mastocytic nodules in patients with raised MC count seem to be pathognomonic of systemic mastocytosis.