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Byline: H. Rico (1), I. Arribas (2), F. J. Casanova (3), A. M. Duce (5), E. R. HernaA'ndez (1), J. Cortes-Prieto (4) Keywords: Key words:Body mass index -- Bone mass -- Bone metabolism -- Gonadal status -- Non-weight-bearing bones -- Total and regional bone mass -- Weight-bearing bones Abstract: Weight and gonadal status are the main determinants of bone mass in women. Because of this it is important to study which influences it more. The effect of weight (expressed as body mass index, BMI) and gonadal status of women on total-body bone mineral content (TBBMC) and regional bone mineral content (BMC) was investigated. A total of 373 normal women (mean age 48.9 +- 13.4 years) were studied: 171 postmenopausal women (mean age 59.3 +- 9.5 years years since menopause 11.3 +- 6.7 years) 76 perimenopausal women (mean age 48.9 +- 2.2 years) and 126 premenopausal women (mean age 34.7 +- 7.4 years). In all the women, TBBMC and regional BMC were determined by dual-energy X-ray absorptiometry. Also biochemical markers of bone metabolism (total alkaline phosphatase and tartrate-resistant acid phosphatase) and serum estrone and estradiol were determined. When the women were stratified by gonadal status and BMI, thin women (BMI &lt 20 kg/m.sup.2) had significantly lower TBBMC and regional BMC, lower gonadal steroid concentration and higher levels of biochemical markers than overweight (BMI 25--30 kg/m.sup.2) and obese (BMI &gt 30 kg/m.sup.2) women, regardless of gonadal status. Overweight and obese women had findings suggestive of increased parathyroid activity, but greater bone mass. Weight rather than gonadal steroid concentration is the main determinant of bone mass in women regardless of gonadal status. Author Affiliation: (1) Department of Medicine, ES (4) Department of Medical Specialties, ES (5) Department of Surgery, ES (2) Central Laboratory, 'Principe de Asturias' University Hospital, University of AlcalaA', Madrid , ES (3) Department of Preventive Medicine and Public Health, Autonomous University of Madrid, Spain, ES Article note: Received: 6 July 2001 / Accepted: 15 November 2001

Byline: H. Rico (1), F. Aguado (1), I. Arribas (2), E. R. Hernandez (2), L. F. Villa (2), C. Seco (2), J. J. Gervas (2) Keywords: Key words:Biochemical markers of bone remodeling -- Body mass index -- Bone mass -- Gonadal status -- Phalangeal bone ultrasound -- Reproductive age Abstract: The behavior of phalangeal bone ultrasound was studied, measured by amplitude-dependent speed of sound (Ad-SOS) in meters per second, in 324 normal women (mean age 48.9 +- 13.7 years) classified by gonadal status (premenopausal, perimenopausal and postmenopausal) and body mass index (BMI, thin, normal, overweight and obese). Ad-SOS differed significantly with gonadal status and BMI (p&lt 0.0001 for all). In the overall group of women, Ad-SOS correlated negatively with age (r=-0.84, p&lt 0.0001), weight (r=-0.16, p&lt 0.005), BMI (r=-0.27, p&lt 0.0001), and tartrate-resistant acid phosphatase concentration (TRAP) (r=-0.35, p&lt 0.0001). The negative correlation remained significant in the groups separated by gonadal status, but to a lesser extent. After adjusting for confounding variables such as age and weight, Ad-SOS was dependent on age (but not on weight or BMI) in the overall group of women and in the gonadal status groups. In conclusion, Ad-SOS values differed significantly with gonadal status and BMI, and correlated negatively with TRAP. The plot of Ad-SOS against age differed significantly with gonadal status as well as BMI. Author Affiliation: (1) Department of Medicine, Radiodiagnostic Service, ES (2) Central Laboratory of the University of Alcala, Madrid, Spain, ES Article note: Received: 31 January 2000 / Accepted: 14 December 2000

Infections of the eye are among the leading causes of vision impairment and vision loss worldwide. The ability of a drug to access the anterior parts of the eye is negligible after systemic administration. Effective drug delivery to the eye is a major challenge due to the presence of protective mechanisms and physiological barriers that result in low ocular availability after topical application. The main purpose of this work was the improvement of the corneal and conjunctival permeation of the antibiotic Ciprofloxacin, a wide spectrum antibiotic used for the most common eye infection, using a self-dissolving polymeric film. Films were prepared by the solvent casting technique, using polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft co-polymer (Soluplus), polyvynyl alcohol, and propylene glycol. Films were homogeneous in drug content and thickness, as demonstrated by adapting the Swiss Roll technique followed by microscopy observation. These films proved in vitro to control the release of the Ciprofloxacin. Ex vivo permeability studies using Franz diffusion cells and porcine cornea and sclera showed an effective permeability of the drug without inducing irritation of the tissues. Films swelled in contact with artificial tears forming an in situ gel over 20 min, which will improve drug contact and reduce the need of multiple dosing. The antibiotic activity was also tested in vitro in five types of bacterial cultures, assuring the pharmacological efficacy of the films. The developed films are a promising drug delivery system to topically treat or prevent ocular infections.

The effects of salmon calcitonin and clodronate were compared in ovariectomised rats. Sixty female Wistar rats ( 260 g in weight) were fed the same diet and had the same living conditions. The rats were divided into the following groups: 15 rats with sham ovariectomy and no drug treatment (Sham-OVX); 45 rats with bilateral ovariectomy subdivided into 15 rats not receiving drug treatment (OVX group), 15 rats treated with subcutaneous salmon calcitonin, 2 U/kg/day every 2 days (OVX + CT group) and 15 rats treated with subcutaneous clodronate, 5 mg/kg/day every 2 days (OVX + Cl group). Sixty days after surgery, the rats were sacrificed and their femurs and fifth lumbar vertebrae were dissected and cleaned of soft tissue. Femur length, vertebral height, and bone mineral content and bone mineral density of the femur and fifth lumbar vertebra by dual-energy X-ray absorptiometry were measured. Calcitonin had a significant and stronger effect in preventing ovariectomy-induced osteopenia in the femur (OVX + CT vs OVX groups, p < 0.0001); both calcitonin and clodronate had a significant effect on the fifth lumbar vertebra, which was greater in the calcitonin group (OVX + CT vs OVX + Cl groups, p<0.005). These findings indicate that calcitonin has a protective effect on both the axial (trabecular bone) and peripheral (cortical bone) skeletons, but clodronate only has a protective effect on the axial skeleton.

Because of the importance of nutrition in the development of bone mass, we studied the nutritional state, and bone state by means of metacarpal radiogrammetric measurements and vertebral morphometry in a group of 40 premenopausal women born between 1960 and 1970, mean age 29 +/- 5 years, and in another group of 40 postmenopausal women born between 1934 and 1944, mean age 55 +/- 4 years. Both groups were considered normal, the main characteristic distinguishing them being that the women born between 1934 and 1944 grew up in a period of widespread malnutrition in Spain and the women born between 1960 and 1970 grew up in a period of normal nutrition. Protein, carbohydrate and fat intake in these two periods differed significantly (p < 0.0001 in the three cases by Fischer's exact test). The values of the metacarpal measurements, anterior height of the dorsal vertebrae from T-4 to T-12, and posterior height from L-1 to L-4 between the premenopausal and postmenopausal groups of women were significantly different (p < 0.001) (Anova test). These findings show the importance of nutrition in the development of bone mass during childhood.

We evaluated the precision of metacarpal radiogrammetry by computed radiography as a technique for bone mass measurement. Measurements obtained using this method were compared with densitometric measurements of total body bone mass using dual-energy X-ray absorptiometry. Our results showed that the coefficients of variation for radiogrammetric measurements were similar in 60 women with osteoporosis and in 100 normal women: 0.7% in both groups for external diameter of the second metacarpal, 2.41% in the normal women and 2.03% in the women with osteoporosis for internal diameter, and 2.3% and 2.4%, respectively, for cortical thickness. Except for external metacarpal diameter, which did not differ between normal and osteoporotic women, all the measurements were smaller in the women with osteoporosis (p < 0.001). The correlation between metacarpal cortical thickness and total body bone mineral content was r2 = 0.462 in the women with osteoporosis, r2 = 0.476 in the controls, and r2 = 0.522 in the two groups combined (all p < 0.001). There was a significant correlation (p < 0.001) between cortical thickness and densitometric metacarpal measurements of both the diaphysis and epiphysis. These results confirm the value of radiogrammetry as a technique for quantitating bone mass under normal and pathological conditions. Additional advantages of the method are minimal radiation dose delivered, possibility for storing the image and data, and technical facility.

Dual energy X-ray absorptiometry measurements of total body bone mineral content (TBBMC), fat body mass (FBM) and fat mass percentage (%FM), lean body mass (LBM) and body weight (BW) were performed on 168 normal postmenopausal females. They were matched regarding life style and habits and had body mass index under 30. Their TBBMCs were correlated with these measurements, with chronological age (CA) and with the number of years since menopause (YSM). There was no correlation between TBBMC and %FM and LBM, but there was with BW (p < 0.001). There was a significant and negative correlation (r = -0.453, p < 0.001) between TBBMC and CA and to a higher range (r = -0.697, p < 0.001) with YSM. Menopausal females over 60 (n = 87) presented less bone mass than younger females (n = 81) (p < 0.01). These data suggest that regarding TBBMC, menopausal onset is a more important factor in bone mass loss, which persists rather markedly even during periods of time far from menopause and that TBBMC depends more on BW than on LBM and FM in women.

Total body bone mineral content (TBBMC), total body bone mineral density (TBBMD), and regional bone mineral content (BMC) were determined with dual energy X-ray absorptiometry and correlated with different anthropometric variables in 324 normal male subjects aged 15 to 85 years, in order to obtain further knowledge of the controversial course of bone mass in males. These subjects showed increased TBBMC and TBBMD up to the age of 25-29 years. A positive and significant (p < 0.001) correlation was observed between TBBMC and TBBMD and with BMC with age (p < 0.001), as well as between age and body weight (p < 0.001) and between the latter and body fat (p < 0.001). Age did not correlate with weight or TBBMC, TBBMD, and regional BMC in subjects older than 29 years, while a significant and positive correlation between body weight and muscle mass was observed with bone mass (p < 0.001). By multiple regression analysis, TBBMC was significantly independent of fat-free mass (FFM) and lean body mass (LBM) (p < 0.01). These findings led us to point out that bone mass increases until the age of 29 years and that changes depend more on weight that on age in men. The rate of bone mass loss with age was 0.23%, that of soft tissue 0.35%, while fat mass increased 0.7% per year.

Bibliographic references seem very controversial regarding the most appropriate anatomical area for bone mass estimation. Since some overlapping in the different bone mass measurements among normal and osteoporotic females has been observed, we have studied the bone mineral content of the pelvic bone through DEXA, and have correlated it with the total body bone mineral content, a highly discriminating measure, in order to observe whether pelvic bone mineral may be a useful measure in bone mass assessment. Pelvic and total body bone mineral values did not decrease until menopause in 104 normal premenopausal females aged 20 to 49 years. On the other hand, these values decreased in normal postmenopausal women (n = 44) aged 50 to 65 years (p < 0.001), with a 16% pelvic bone mineral content and an 11% total body bone mineral content decrease. Osteoporotic females (n = 30), showed lower values for both levels than normal postmenopausal ones (p < 0.001), with a 54% pelvic and a 24% total decrease. A 15% overlap was observed when pelvic values between normal postmenopausal and osteoporotic females were compared. The greater percentage decrease in pelvic BMC compared to total body bone mineral content and the lower overlap observed suggest that the pelvis may be an ideal anatomical area for bone mass evaluations.

In the present, cross-section study, a total of 185 normal premenopausal females--aged 15 through 19 years (n = 40), 20 to 29 years (n = 60), 30 through 39 years (n = 40) and 40 to 49 years (n = 45)--were assessed in order to observe and evaluate the total body bone mineral content and the regional body mineral content of different anatomical regions (head, trunk, arms and legs), when the bone mass peak is established in women and its course during premenopause. All subjects underwent bone densitometry with dual energy X-ray absorptiometry with a Norland XR-26 bone densitometer. No differences between groups were found in total body bone mineral and regional bone mineral content values. Total body bone mineral values (mean +/- SD) were 2546 +/- 461 g and 2691 +/- 499 g in the 15-19 year-old group and 40-49 year-old group respectively. The regional bone mineral content values for the same age group were 495 +/- 75 g and 499 +/- 89 g for the head, 1007 +/- 254 g and 1043 +/- 212 g for the trunk, 327 +/- 74 g and 336 +/- 81 for the arms, and 860 +/- 167 g and 811 +/- 146 g for the legs. The results of this study indicate that the peak bone mass is reached at the age of 20 years and that it remains stable in the premenopausal eugonadal females.

It has been reported that metacarpal morphometry does not correlate with iliac crest histomorphometry in patients with hip fractures. Such disagreement led us to study the correlation between both types of measurements on 35 patients who had suffered hip fracture. We observed a significant correlation between metacarpal morphometry and iliac crest cortical width (p less than 0.001), and to a lesser degree with the trabecular bone volume (p less than 0.01). The same was also true if we assessed separately the patients with cervical or trochanteric hip fractures.

In an open study, we have assessed the bone/soft tissue uptake index in recent osteoporotic vertebral collapse using scintigraphy. The evolution of these cases was followed-up at 6 months in 22 patients treated with 100 IU of salmon calcitonin plus 500 mg of elemental calcium/10 days per month and in 18 patients treated with 500 mg of elemental calcium only on a daily basis. There were no index differences between groups prior to treatment. At six months, the group treated with calcitonin plus calcium showed a significant decrease from 10.2 +/- 6.4 to 3.2 +/- 1.1 (p less than 0.001), while the calcium only group did not show any significant changes (12.1 +/- 6.6 vs 9.2 +/- 4.6), considering that there were significant differences between groups (p less than 0.001). On a mid-term basis, these results have shown the values of the bone/soft tissue index in the follow-up of osteoporotic vertebral collapse.

Osteopenia observed in corticotherapy is due, among other causes, to a decrease in bone formation as can be shown by a steroid-induced osteocalcin decrease. Although various treatments have been proposed there is no agreement as to which one is the best. Two such treatments, sodium fluoride and vitamin D administration increase osteocalcin levels. We treated a group of 12 patients under corticoid therapy (mean dose 16 mg per day) with 50 mg/day p.o. sodium fluoride, and determined osteocalcin levels before and two weeks after sodium fluoride treatment. Similarly, another group of 9 patients with a similar mean steroid dose was treated with 0.5 micrograms/day of 1 alpha (OH)2D3 in order to assess the effect of this vitamin on osteocalcin and to determine which was the best treatment. Both groups were compared with respective control groups. A significant osteocalcin increase was observed in the control groups (p less than 0.001); similar significance was observed in the sodium fluoride group, whereas a lower significance (p less than 0.01) was observed in the vitamin D group. These results suggest that sodium fluoride could be more effective than vitamin D in the treatment of steroid-induced osteopenia.

To determine whether the osteopenia of rheumatoid arthritis (RA) is due to reduction of trabecular bone mass (TBV) and/or cortical width (CW), we evaluated these parameters by bone histomorphometry; we also measured the calciotropic hormones parathormone(PTH) and calcitonin (CT), vitamin D [25(OH)D] and the biological markers of bone remodeling in a group of patients with RA. Study subjects were divided into Group C - premenopausal patients, and Group A - menopausal patients and men of the same ages. These groups were compared to two age-matched control groups, B and D. In both A vs. B and C vs. D, TBV and CW were significantly lower in patients. There were no differences in PTH or CT, but 25(OH)D was significantly reduced, and BGP, OHP/Cr and AP were raised in patients. Patients also exhibited TBV loss in more than 55% and CW loss in more than 98%. These changes suggest that the decline in bone mass, mainly cortical, but also trabecular, is due to increased bone turnover and enhanced resorption and seem to reflect intrinsic alterations of RA.

The transition of blastospores to the mycelial phase in Candida albicans was induced after the blastospores were kept at 4 degrees C for several hours and then transferred to a fresh medium prewarmed at 37 degrees C. Glucan was the most abundant polymer in the wall in the two morphogenetic forms but the amount of chitin was higher in the mycelial form than in blastospores. Efficient protoplasting required reducing agents and proteases together with beta-glucanases (zymolyase). Protein synthesis in regenerating protoplasts was initiated after about 30 min. Chitin synthetase, initially very low, was incorporated in important amounts into cell membranes mainly in a zymogenic state. After a few hours chitin was the most abundant polymer found in the aberrant wall of the regenerating protoplast.

The hormonal variations in postmenopausal osteoporosis are not precisely defined. The duration of the menopause and other factors, such as the weight of the patients, may be of significance. Having a basic criterion of uniformity in weight, sixty postmenopausal women were studied in regard to the following aspects: urinary hydroxyproline, estrone, estradiol, parathyroid hormone, thyroxine, triiodothyronine, thyroid stimulating hormone, cortisol and metacarpal cortical area/total area. They were divided into: Group A: 15 patients with osteoporosis and five years since menopause; Group B: 15 patients without osteoporosis (age-matched with group A); Group C: 15 patients with osteoporosis and more than ten years since menopause; and Group D: 15 patients without osteoporosis (age-matched with Group C). In the group with postmenopausal osteoporosis (A and C) there is a significant increase in urinary hydroxyproline/creatinine and a significant decrease of the cortical area/total area when we compared them with age-matched groups. The hormonal values do not vary significantly among the four groups. Ours results indicate an increase of bone resorption as a cause of postmenopausal osteoporosis. The hormonal variations, if any, cannot be related to basal values.

The clinical features of a new patient with dysplasia epiphysialis multiplex are reported. Similar symptoms are present in four members of the family. This disease seems to be inherited as a simple dominant Mendelian trait. The disease mainly affects the epiphyses of the long bone and nearly always begins with pain in the hip-joint. Our patient presented radiological features of osteoporosis with calciotropic hormones within normal range and with a low trabecular bone volume. This histomorphometric bone study shows a low bone turnover osteoporosis, which suggests an altered trabecular development with a greater clinical expression in the epiphyses.

A study was made of 26 patients diagnosed as phase I reflex sympathetic dystrophy. In all of them, a bone:soft tissue uptake index was quantified by scintigraphic scanning before treatment and 3 months later. Eighteen patients were treated with 100 MRC units salmon calcitonin, followed by 500 mg elemental calcium 4 hours after hormone administration. The treatment was administered 10 days a month separated by intervals free of therapy. The other 8 patients were treated without interruption with 500 mg naproxen every 12 hours. In the group treated with calcitonin and calcium, the uptake index declined from 13.3 +/- 8.2 to 4.1 +/- 1.8 (p less than 0.001). The uptake index rose from 2.1.3 +/- 17.7 to 31.1 +/- 23.0 (NS) in the naproxen group. Using the Student t-test for paired samples to evaluate individual changes, a highly significant difference was reached (p less than 0.005) in the calcitonin-calcium group. The difference was also significant (p less than 0.01) in the naproxen group, but it was negative (t = 3.620). These results confirm the efficacy of treating reflex sympathetic dystrophy with calcitonin and calcium and the superiority of this treatment as compared with nonsteroidal anti-inflammatory drugs.

Two cases of late hypophosphatemic osteomalacia are described: a male aged 30 who had the disease since he was 22 and a woman of 23 who had the disease since she was 14. Both presented with myopathy and bone pain, and showed hypophosphatemia, hyperglycinuria, reduced tubular phosphate reabsorption (TPR), increased hydroxyprolinuria and normal iPTH and iCT values. Radiologically the male had no Looser's zones and the woman did. Bone biopsy confirmed hypophosphatemic osteomalacia. Both cases were treated with vitamin D and oral phosphate and no improvement was observed. When treatment with 25(OH)D3 was initiated, no improvement was seen and afterwards this was combined with treatment using 1.25(OH)2D3 and from this time on a clinical improvement of the myopathy became evident in both patients. In the woman, healing of the bone lesions occurred at the same time as that of the myopathy, whereas in the male the bone lesions became worse. Healing of the myopathy was only obtained when treatment with 1.25(OH)2D3 was begun. Both patients had reduced values of 2.3 erythrocytic DPG and low level of serum phosphorus when the myopathy was cured, which suggests a lack of effect of 2.3 DPG or serum phosphorus as a cause of the myopathy. Although this had been attributed to a deficiency in the function of 25(OH)D3, the response to 1.25(OH)2D3 and due to the effects of this metabolite on calcium transport in muscle, suggests that the myopathy which occurs in late hypophosphatemic osteomalacia is a result of deficiency or resistance to the muscular effect of this metabolite. We cannot explain the lack of bone healing in the man and further therapeutic studies are required.