Congenital erythropoietic porphyria: skeletal manifestations and effect of pamidronate treatment.

Congenital erythropoietic porphyria (CEP) is a rare disorder of heme biosynthesis. Skeletal abnormalities have been described in patients with this disease. We report a 25-year-old woman with osteodystrophy from CEP. On examination, mild hepatosplenomegaly, multiple hyperpigmented scars, hypertrichosis, erythrodontia and red coloration of urine were found. Biochemical studies showed increased serum levels of alkaline phosphatase, fasting and total 24-h urinary calcium excretion. Serum 250H vitamin-D concentration was low due to avoidance of sun exposure. Skeletal radiographs disclosed marked vertical and horizontal trabecular pattern and biconcavity of most of the dorsal and lumbar vertebral bodies. Several round sclerotic lesions (1-3 cm in diameter) were seen in the skull, pelvis and one lumbar vertebrae. The sclerotic lesions were augmented in size and number compared to X-rays obtained 8 years before. Bone mineral density (evaluated by DEXA) was markedly reduced at the spine and moderately diminished at the proximal femur and total skeleton. Treatment for 11 months with pamidronate (and the addition of hydrochlorotiazide for the last 6 months) reduced to normal values the serum levels of alkaline phosphatase and fasting urinary calcium. The 24-h urinary excretion of calcium and hydroxyproline were also decreased. The BMD increased in all the skeletal areas with presumably hyperactive bone marrow: spine, head, ribs and pelvis (and total skeleton), but did not change at the extremities and diminished at the femoral neck. Patients with CEP may present osteodystrophy characterized by sclerotic lesions and osteopenia, most likely due to accelerated bone turnover in areas of active bone marrow.(ABSTRACT TRUNCATED AT 250 WORDS)

Serum levels of 25-hydroxyvitamin D in a year of residence on the Antarctic continent.

OBJECTIVE: Since exposure to sunlight is the main source of vitamin D in human beings and skin photosynthesis decreases markedly as the latitude increases, we studied the changes in serum 25-hydroxyvitamin D (25(OH)D) levels in young healthy men who lived in the Antarctic Continent during 1 year. DESIGN: Blood was drawn in the fasting state every 2 months from March 1990 to January 1991 to determine the serum levels of calcium, alkaline phosphatase and 25(OH)D. SUBJECTS: 19 healthy volunteers, who left Buenos Aires (34 degrees S) during the 1990 summer, arriving at the Antarctic bases at the end of January (Belgrano) and in mid-March (San Martín) and stayed there up to summer 1991. RESULTS: Serum calcium did not change significantly throughout the year. Serum alkaline phosphatase levels were not different comparing the beginning to the end of the year, but autumn and winter levels were lower (P < 0.05). At Belgrano Base the serum 25(OH)D levels (ng/ml) decreased from (mean +/- SD) 18.7 +/- 7.4 (March) to 10.0 +/- 4.3 (July) (P < 0.005) and did not recover for the rest of the year. At San Martín Base the serum 25(OH)D levels descended from 22.0 +/- 5.4 in March to 12.2 +/- 3.7 in August (P < 0.02) and did not increase even at the beginning of summer (January) except in two men with frequent outdoor activities. CONCLUSIONS: The levels of 25(OH)D of healthy men living in the Antarctic continent decreased to approximately 46% of the initial values and did not increase even at the onset of summer. Further studies should determine the effect of these changes upon calcium-regulating hormones and bone metabolism.

Bone mineral density response to long-term bisphosphonate therapy in fibrous dysplasia.

Fibrous dysplasia of bone is a rare disease related to a genetic mutation in which bone formation at osseous sites is altered. In the last few years, bisphosphonates have become one of the choice drugs to treat this disease. A 26-yr-old woman presented after 6 wk of spontaneous right leg pain owing to a fissure fracture of the right femoral neck. She reported precocious puberty at the age of 2, with diagnosis of McCune-Albright syndrome. Radioisotope bone scanning, radiographic, biochemical, and densitometric studies were performed. Treatment with bisphosphonates was started because bone turnover biochemical markers were abnormal. Oral olpadronate followed by iv pamidronate substantially decreased bone resorption. Bone mineral density (BMD) of total skeleton and subareas was assessed by dual X-ray absorptiometry (DXA) throughout the 5 yr of treatment. At the end of this period, BMD of the total skeleton had increased 6.2%. However, BMD of the areas most affected by fibrous dysplasia, the legs and pelvis, had increased 12.7 and 11%, respectively. Region of interest analysis of individual bones of the legs performed with the total skeleton scan revealed that BMD of the areas most affected by fibrous dysplasia was lower than that of the less affected contralateral bones. During the first 3 yr, treatment with bisphosphonates substantially increased BMD of the right femur and tibia (22 and 28%, respectively). After that, values seemed to stabilize. DXA evaluation of the total skeleton and its subareas was useful to evaluate the efficacy of bisphosphonate treatment. Moreover, the plateau observed in BMD values after 3 yr of treatment suggests that treatment could have been discontinued when the densitometric values stabilized.

Body composition of professional football (soccer) players determined by dual X-ray absorptiometry.

A three-compartment body composition analysis of 42 professional football (soccer) players and 33 age- and body mass index-matched control subjects was determined by dual X-ray absorptiometry (DXA). The equipment provided a direct measurement of fat, lean, and bone mass. Fat mass was significantly higher in the controls subjects whereas lean mass and bone mass were markedly higher in the players. The percentage of body weight fat varied from 6.1 to 19.5% in the football players and from 9.1 to 29.9% in the control subjects. The respective averages were 12.0 +/- 3.1 and 19.2 +/- 5.6% (p < 0.001). The midfielders had a significantly higher percentage of fat (13.6 +/- 3.3%) than backs or forwards (11.1 +/- 2.8 and 11.0 +/- 2.3%, p < 0.05 and p < 0.06, respectively). In the football players, the correlation between age and fat mass was significant (r = 0.53, p < 0.001), whereas there was no correlation between fat and age in the control subjects (r = 0.13 p > 0.1). This article provides, for the first time, DXA analysis of body composition of football players in relation to their age and function. The results should be of interest to coaches because they will help improve athletes' performance.

[Winter serum levels of 25-hydroxy-vitamin D in Ushuaia and Buenos Aires]. / Niveles séricos invernales de 25-hidroxi-vitamina D en Ushuaia y Buenos Aires.

Public Health Annals recording diagnosis of nutritional rickets in patients admitted in Public Hospitals disclosed that from birth to age 14, in the period 1980-1981, the incidence was 2.7 higher in the Patagonia (latitude 39 degrees S to 55 degrees S) compared with the Pampeana Region and 8.5 higher than in the rest of the country. After informed parental consent 37 healthy children of Buenos Aires (34 degrees S) with an age of (Av +/- 1 SD) 7.0 +/- 1.2 years, 29 with an age of 13.1 +/- 1.5 years and 63 of Ushuaia (55 degrees S) with an age of 7.1 +/- 0.8 years were studied at the end of winter (August). Serum levels of 25-OH-D were as follows (mean +/- SE): Buenos Aires: 21.1 +/- 2.03 ng/ml (Average: seven years old), 19.0 +/- 1.18 ng/ml (children of thirteen years old) and Ushuaia: 9.3 +/- 0.64 ng/ml (p less than 0.001) (Fig. 2). Serum levels were below 8 ng/ml in 52% of the children in Ushuaia but only in 9% in Buenos Aires. Serum calcium and alkaline phosphatase levels were similar in the two groups but serum phosphate was higher in Ushuaia (Table 1). The calcium intake was greater in Ushuaia (811 +/- 49 mg/day) than in Buenos Aires (634 +/- 61 mg/day) and was correlated with 25-OH-D levels in children of Ushuaia (r = 0.50, p less than 0.001) but not in Buenos Aires (r = 0.08). The main source of calcium intake was vitamin D fortified milk. These results disclosed a significantly diminished level of serum 25-OH-D in Ushuaia.(ABSTRACT TRUNCATED AT 250 WORDS)

[Osteoporosis in all young daughters of a mother with multiple osteoporotic fractures. A case of familial osteoporosis]. / Osteoporosis en todas las hijas jóvenes de una madre con múltiples fracturas osteoporóticas. Un caso de osteoporosis familiar.

We herein describe a family whose female members are all osteoporotic: a postmenopausal mother and her three premenopausal daughters. The mother aged 60 presented axial and peripheral fractures, and very low bone mineral density (BMD). She reported that her grandmother had suffered a hip fracture. The eldest daughter aged 30 suffered multiple vertebral fractures during pregnancy and lactation associated with very low BMD. In view of these observations, the other two daughters aged 29 and 27 years respectively were evaluated. BMD was found to be severely diminished according to densitometric values for osteoporosis established by WHO, but they had no history of bone fractures. Probably the strong genetic component in bone mass is responsible for the severely diminished BMD observed in all the women in this family, as well as the occurrence of bone fractures in two of them. To our knowledge, there are no similar reports in the literature. Our results evidence the importance of evaluating bone mass in the offspring of an individual presenting severe osteoporosis, in order to detect family members with low bone mass and at high risk of developing bone fractures.

[Nutritional status of vitamin D in mothers and neonates of Ushuaia and Buenos Aires]. / Estado nutricional de vitamina D en madres y neonatos de Ushuaia y Buenos Aires.

Serum levels of calcium, phosphorus, total alkaline phosphatase (AP) and 25 hydroxyvitamin D (250HD) were measured at the end of the winter in Group 1 (Ushuaia, latitude 55 degrees S): 16 women (24-48 hs postpartum serum blood) and 20 neonates (cord blood) and in Group 2 (Buenos Aires, latitude 34 degrees S) 21 women (24-48 hs postpartum serum blood) and their 21 neonates (cord blood). The neonatal serum calcium and phosphorus were higher and the neonatal serum AP and 250HD level were lower than maternal levels in both groups (Table 1 and 2). Serum levels of 250HD were diminished (< 8 ng/ml) in 62% of the mothers and 81% of the neonates of Ushuaia and in 24% of the mothers and 16% of the neonates of Buenos Aires (figure 1). Neonatal serum 250HD levels correlate with maternal serum 250HD levels in the paired group of Buenos Aires (r = 0.65, p < 0.003) (Figure 2). In Ushuaia the serum 250HD levels (X +/- SD) in neonates (3.9 +/- 2.7 ng/ml) and in mothers (6.3 +/- 4.8 ng/ml) were lower than in Buenos Aires (neonates: 11.3 +/- 6.0 ng/ml and mothers: 14.4 +/- 8.4 ng/ml, p < 0.001). Maternal serum calcium levels were lower in Ushuaia (8.7 +/- 0.8 mg/dl) than in Buenos Aires (9.2 +/- 0.4 mg/dl) (p < 0.05). In conclusion, 1) In Ushuaia pregnant women and their neonates had a deficient nutritional state of vitamin D. Preventive administration of vitamin D would probably be beneficial.(ABSTRACT TRUNCATED AT 250 WORDS)

Regression of calcinosis during diltiazem treatment in juvenile dermatomyositis.

An 8-year-old girl with juvenile dermatomyositis (DM) developed dystrophic calcifications 26 months after diagnosis. She also had severe steroid induced bone loss (osteoporosis). The calcifications turned into generalized heterotopic calcinosis with an exoskeleton-like pattern, despite successful treatment of her myopathy with methylprednisolone and immunosuppressive drugs. She was subsequently treated with oral diltiazem (5 mg/kg/day) to control calcinosis and oral pamidronate (4 mg/kg/day) in addition to calcium and vitamin D supplementation, which she had been taking for 3 years. After 21 months of treatment, clinical and radiological examination revealed dramatic regression of the calcinosis. Bone mass reached normal levels, as determined by bone absorptiometry. Diltiazem alone or in combination with other drugs could be a useful therapy in patients with juvenile DM and pronounced calcifications.

Peripheral bone mass is not affected by winter vitamin D deficiency in children and young adults from Ushuaia.

Low vitamin D levels in elderly people are associated with reduced bone mass, secondary hyperparathyroidism, and increased fracture risk. Its effect on the growing skeleton is not well known. The aim of this study was to evaluate the possible influence of chronic winter vitamin D deficiency and higher winter parathyroid hormone (PTH) levels on bone mass in prepubertal children and young adults. The study was carried out in male and female Caucasian subjects. A total of 163 prepubertal children (X age +/- 1 SD: 8.9 +/- 0.7 years) and 234 young adults (22.9 +/- 3.6 years) who had never received vitamin D supplementation were recruited from two areas in Argentina: (1)Ushuaia (55 degrees South latitude), where the population is known to have low winter 25OHD levels and higher levels of PTH in winter than in summer, and (2)Buenos Aires (34 degrees S), where ultraviolet (UV) radiation and vitamin D nutritional status in the population are adequate all year round. Bone mineral content (BMC) and bone mineral density (BMD) of the ultradistal and distal radius were measured in the young adults. Only distal radius measurements were taken in the children. Similar results were obtained in age-sex matched groups from both areas. The only results showing significant difference corresponded to comparison among the Ushuaian women: those whose calcium (Ca) intake was below 800 mg/day presented lower BMD and BMC values than those whose Ca intake was above that level (0.469 +/- 0.046 versus 0.498 +/- 0.041 g/cm(2), P < 0.02; 3.131 +/- 0.367 versus 3.339 +/- 0.386 g, P < 0.05, respectively). In conclusion, peripheral BMD and BMC were similar in children and young adults from Ushuaia and Buenos Aires in spite of the previously documented difference between both areas regarding UV radiation and winter vitamin D status. BMD of axial skeletal areas as well the concomitant effect of a low Ca diet and vitamin D deficiency on the growing skeleton should be studied further.

Seasonal variations of 25 hydroxyvitamin D and parathyroid hormone in Ushuaia (Argentina), the southernmost city of the world.

Serum levels of calcium, phosphorus, alkaline phosphatase, 250HD, 1.25(OH)2D and PTH were studied in a group of 42 children aged 8.5 +/- 1.8 years (X +/- SD) from the city of Ushuaia (latitude 55 degrees S), at both the end of the winter and the end of summer. Calcium, phosphorus, alkaline phosphatase and 1.25(OH)2D serum levels were not different in summer and winter. The levels of serum 25OHD were significantly higher in summer (18.4 +/- 7.3 ng/ml) than in winter (9.8 +/- 3.8 ng/ml P < 0.001). The levels of 25OHD in children with fair or dark skin were similar in winter but were significantly higher in children with fair skin in summer (20.0 +/- 7.2 ng/l vs 15.3 +/- 5.1 ng/ml (P < 0.05). Serum levels of PTH were higher in winter (58.2 +/- 30.5 pg/ml) than in summer (47.9 +/- 28.3 pg/ml) (P < 0.03). The results demonstrate the existence of a population with low serum levels of 25OHD in winter. The higher levels of PTH in winter when serum 25OHD levels are lower could be the cause of the lack of seasonal variation in serum calcium and 1.25(OH)2D levels. Further studies are needed to establish whether these changes besides increasing the incidence of rickets, could also affect the mineral density of the skeleton in the population of this vitamin-D-deficient area.

Bone mineral density of the spine and radius shaft in children with X-linked hypophosphatemic rickets (XLH).

X-linked hypophosphatemic rickets (XLH) is characterized by inadequate skeletal mineralization. The bone mineral density (BMD) of the radius shaft and the lumbar spine was determined in 13 children with XLH. Ten patients were on treatment, whereas three patients had discontinued treatment 20-32 months prior to this study. Two of them had radiological evidence of rickets. The radius shaft BMD was significantly diminished: Z score was -1.33 +/- 0.89 (P less than 0.001), while the BMD of lumbar spine was significantly augmented (Z score +1.95 +/- 1.17, P less than 0.001). A positive correlation was found between the Z scores for the BMD of the radius shaft and spine. The two patients with overt rickets had lower radius shaft BMD values and a lesser increment of BMD of the spine. The BMD deficit of cortical bone may be related to the lack of efficacy of the treatment and/or to an intrinsic defect of the bone on this disease. On the other hand, the augmented BMD of the lumbar spine might reflect the overabundance of partially mineralized osteoid. The determination of the BMD of the radius shaft by SPA was a sensitive method for detecting abnormalities of the bone mass in XLH patients under treatment without radiological signs of rickets.

Vertebral compression fractures at the onset of acute lymphoblastic leukemia in a child.

A child with acute lymphoblastic leukemia, spinal osteoporosis with vertebral compression fractures, and hypercalcemia appearing early in the course of the hematologic disease was followed for two and a half years. Bone mineral density (BMD), measured by single photon absorptiometry at the radial shaft, was within normal limits for age and sex. However, x-rays of vertebrae and vertebral BMD, measured by dual photon absorptiometry, showed marked demineralization. Despite leukemic remission, the spinal osteoporosis became worse and the patient required aggressive treatment for eight months. Treatment included 50 units of calcitonin subcutaneously every other day, 1,000 mg/day of oral calcium, and 3,000 IU/day of vitamin D. The back pain disappeared quickly, and laboratory controls showed a significant diminution of bone turnover. No new compression fractures occurred. Eighteen months later, the patient continued in remission and menarche had occurred. Dual photon absorptiometry revealed a significant "catch up" of the lumbar spine BMD. X-ray examination showed a marked remodeling of the vertebral bodies. BMD measurements in this child indicate that bone loss affected the trabecular bone compartment or occurred only at active bone marrow sites. The rapid clinical amelioration and objective biochemical, densitometric, and radiologic evidence of bone improvement warrant further clinical trials on similarly affected patients.

Professional football (soccer) players have a markedly greater skeletal mineral content, density and size than age- and BMI-matched controls.

The total skeletal bone mineral content (BMC), bone mineral density (BMD), bone size, and body composition were measured by dual-energy x-ray absorptiometry (DXA) in all professional male football players of a 1st division team (n = 24) and age- and BMI-matched (n = 22) controls (less than 3 hours of recreational sport activities per week). Average (+/- 1 SD) age of the athletes was 22.6 +/- 2.5 years. Intensive training is conducted during 48 weeks a year for 20-22 hours/week. The length of the registered playing career before the study was 8.2 +/- 2.7 years. Total skeleton BMC was 18.0% (P < 0.001) greater in the football players. The difference resulted from the sum of 5.2% (P < 0.02) increment of bone size and 12.3% (P < 0.001) increment of BMD. The analysis of skeletal subareas revealed that the difference of the BMC and BMD was greater at the level of the pelvis and legs compared with the arms or trunk. The BMC and BMD of the head was equal for both groups. Also, the bone size of the legs and pelvis was significantly greater for the players compared with controls; there was no difference at the level of the arms or head. Within the group of football players the increment of total skeleton BMD was similar in the young players, with less than 7 years of practice (age 20.6 +/- 0.9 years) compared with relative older players (age 24.6 +/- 1.9) with more than 7 years of practice. Lean body mass was significantly greater in the players (63.3 +/- 4.0 kg) compared with the controls (56.7 +/- 3.6, P < 0.001) whereas fat mass was markedly lower (9.4 +/- 2.9 kg versus 14.9 +/- 6.3 kg), P < 0.002). The BMD of the controls was significantly correlated to total weight, height, and lean mass whereas the BMD of the players was only correlated to muscle mass. The calcium intake from dairy products was similar in both groups. The range of calcium intake was wide among the players (184-2519 mg/day) but it was not significantly correlated to BMD (r = 0.03). In conclusion, male professional football players develop a significant increment of BMC as a result of increased bone size and density. This is already present at the end of the second decade and maintained at least to the end of the third decade in active players. As in other high impact loading sports, the effect on area is specific involving mainly the pelvis and legs. The increment was totally unrelated to the calcium intake from dairy products. The fate of the increased BMC after intensive training is discontinued should be assessed. However, if the findings of the present cross-sectional study are supported by detailed longitudinal investigations, the presently reported observations might be important for the prevention of future osteoporotic fractures.

Is it necessary to screen for celiac disease in postmenopausal osteoporotic women?

Decreased bone mass is a frequent finding in celiac patients, and subclinical celiac disease (CD) appears to be unusually overrepresented among patients with idiopathic osteoporosis. Since silent CD may be more common than previously believed, it has been suggested that all osteoporotic patients should be checked for occult CD. The aim of this study was to explore the prevalence of CD in a well-defined population of postmenopausal osteoporotic women. We evaluated 127 consecutive postmenopausal patients (mean age: 68 years; range: 50-82 years) with verified osteoporosis. The observed prevalence of CD in this group was compared to that observed in a group of 747 women recruited for a population-based study. The screening algorithm used to diagnose CD was based on a 3-level screening using type IgA and IgG antigliadin antibodies (AGA) in all the patients (1st level) followed by antiendomysial antibodies (EmA) and total IgA (2nd level) of samples testing positive, and intestinal biopsy of positive cases (3rd level). At the end of the serological screening, only 1 of 127 osteoporotic women was eligible for jejunal biopsy showing a characteristic celiac flat mucosa (prevalence 7.9 x 1,000; 95% CI 0.2-43.1). In addition, CD was diagnosed in 6 of 747 women of the population-based study (prevalence: 8.0 x 1,000; 95% CI 3.3-18.3). There was no significant difference between the two groups. Therefore, our study showed that the prevalence of CD in postmenopausal osteoporotic women was lower than that reported in previous studies and similar to that of the general population. In conclusion, although the relatively small size of the group tested does not allow us to be conclusive, the results suggest that a case finding policy in postmenopausal osteoporosis would have a high cost/benefit ratio except for patients not responding to conventional therapies, or presenting borderline laboratory results.