International Congress Series 1237 (2002) 219 – 229
Zincuria and zincemia in postmenopausal osteoporosis Freddy Contreras, Nelson Simonovis, Christian Fouillioux, Alejandra Bolı´var, Jose L. Cevallos, Edwin Lezama, Manuel Velasco* Aportado Postal 76333, El Marques, Caracas A 1070, Venezuela
Abstract Minerals and trace elements are essential for human health, especially during the growing period and old age. Zinc, as an essential element, has been considered necessary for the growth and stimulation of bone formation. Several authors have demonstrated an association between osteoporosis, urinary zinc excretion and high blood zinc levels suggesting that the changes in bone metabolism are the consequences of increased bone reabsorption in osteoporosis. To carry out this study, we selected a group of 62 females with similar characteristics following the inclusion and exclusion pre-established criteria. To make two comparative groups, determination of bone density was made to the initial group and according to these results, we obtained: (1) group A who were 32 postmenopausal healthy women, with a period of at least 3 years since their last menstrual period (LMP) and evidence of osteoporosis made by determination of bone density, and (2) group B who were 30 postmenopausal non-osteoporotic healthy women. From both groups, we obtained blood sampling for the determination of zinc levels. Group A showed higher values (mean F S.D. = 2.13 F 0.41) when compared with group B (mean F S.D. = 1.44 F 0.42) with t value of 6.223 and p < 0.0001. When we compared urinary zinc excretion in both groups, t and p values showed significant differences. We conclude that blood zinc levels and urinary zinc excretion are biochemical markers with high reliability to determine bone reabsorption for the assessment and diagnosis of osteoporosis in postmenopausal women. D 2002 Elsevier Science B.V. All rights reserved. Keywords: Osteoporosis; Blood zinc levels; Urinary zinc excretion; Bone mass; Menopause
*
Corresponding author. E-mail address:
[email protected] (M. Velasco).
0531-5131/02 D 2002 Elsevier Science B.V. All rights reserved. PII: S 0 5 3 1 - 5 1 3 1 ( 0 1 ) 0 0 5 8 8 - X
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1. Introduction Osteoporosis is a systemic skeletal bone disease characterized by low bone density and deterioration of the microarchitecture of the bone tissue, with the consequent increase of the fragility and the susceptibility for bone fractures [1]. Histologically, the problem is characterized by a decrease in the thickness of the cortical layer and in the number and size of the trabecules of the spongy bone [2]. The cortical bone, the compact layer that forms the external cover of the bone, represents 80% of the mature skeleton and the trabecular bone (spongy); it consists of a thin series of badges that form the interior net of the bone and represents the 20% remaining [3]. The cortical bone prevails in the dia´fisis of the long bones and the trabecules in the vertebras, pelvis and plane bones, and in the epı´fisis of the long bones [4]. After the end of the lineal bone growth, the bone mass increases for radial growth until approximately 30 years of age. The maximal bone reserve that an individual obtains is denominated pick of bone mass (OMP), generally reached between the 20 and 30 years of age, which is influenced by the age, sex, genetic factors, hormonal status, exercise and the calcium diet [5]. Starting from here and after a transitory period of stability, the bone loss related with the age begins [4]. Immediately after the menopause, the loss of bone mass accelerates, being able to reach during the first 5 years of the menopause at an annual rate of loss from 1% to 5% [5]. Osteoporosis affects the postmenopausal women with more frequency in a woman– man relationship, which can vary between 3 and 8:1, or 3 to 8 women for each man. The incidence of osteoporosis is not sufficiently established; nevertheless, an incidence of 25% is pointed out for women older than 45 years [6] and 50% for women older than 60 years of age [7]. In accordance with the data published by the World Health Organization (WHO) [8], the number of 65-year-old persons has increased considerably in the last years, being at the present time this population group of 380 million people, representing 7% of the total population of the world and of this, 80 million are older than 80 years. Osteoporosis is the most common metabolic bone disease [9], although its real prevalence is not still clarified. It affects among 20 to 25 million residents in the United States, and it is present in near one of four women older than 65 years [9]. Every year, 1.3 million bone fractures occur related with osteoporosis (12 –20% are hip fractures) [10]. A minimum of 50% of the women has the probability of suffering spontaneous bone fractures as a consequence of the postmenopausal osteoporosis [11]. The developed countries have populations older than 65 years between 10% and 17%. The total population of the world grows to an annual rate of 1.7%, and of this, 60 and more years grows yearly to a ratio of 2.5%. In accordance with the projections, in the world, the number of hip fractures will increase markedly in next half century, especially in Asia and Latin America, making osteoporosis a problem of world public health [12]. The population’s total increment in the region will be characterized every time by a relation bigger than the people of advanced age, accompanying this process with the increment in the expectancy of life which is at the moment located in 71 years for the woman. In 1998, the expectancy of life in Venezuela was 69 and 75 years for men and women, respectively [13]; according to the last census data for the year 1990 and the projections
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for 1998 [14], the country has a population of 23,245,435 inhabitants and 8.9% of the population, that is to say 2,068,085, is constituted by women among 45 and more years of age, and 1,532,019 of 50 or more years. For the year 2035, the Venezuelan total population’s projection will be 38,192,162 inhabitants with a female population of 19,141,192. These figures indicate that for the year 2035 in Venezuela, one of each three women will be climacteric or postmenopausal. This group for their age and postmenopausal condition is at risk to suffer the disease, with the consequent decrease of the quality of life, labor inability, loss of the productivity and increase in the costs of the medical care, which constitutes a problem of public health in our country. By virtue of the increment in the expectancy of our population’s life and since 50% of the women has the probability of suffering spontaneous fractures as a consequence of the postmenopausal osteoporosis [11], it becomes necessary to determine a useful parameter as biochemical indicator of bone reabsorption in osteoporotic postmenopausal women. The objective of this study was to determine the relationship between the zincuria and zincemia levels in postmenopausal women with appropriate bone mass when comparing them with same determinations in osteoporotic women and, simultaneously, to determine the value of the zincuria and the zincemia as biochemical indicators of bone reabsorption in postmenopausal osteoporosis.
2. Patients and methods For the development of this research, a study of crosswise type of occurrence was designed; the population, scope of the investigation, was undertaken in patients that attended the out-patient clinic of Internal Medicine of the University Hospital of Caracas, between January and November of 1998, to whom we applied the inclusion and exclusion criteria settled down to select a group of patients with homogeneous properties (a pair among subject of study). They were obtained in this manner: 62 patients with similar properties were carried out with BMD, a test that allowed to divide the population in two groups: group A constituted of 32 healthy postmenopausal women, with a minimum period of 3 years of finalization of their last menstrual period, with diagnosis of osteoporosis evidenced by BMD and have completed inclusion criterion; and group B constituted of 30 healthy postmenopausal women, with bone mass adapted by BMD and have meet the established criteria. In both groups, an intentional or addressed sampling to the subjects was carried out that completed the following exclusion criteria: (1) alcoholic habit (any quantity); (2) small body structure (weight V 40 kg and/or body mass index (BMI) smaller or similar to 19); (3) associated diseases: tirotoxicosis, Cushing syndrome, rheumatoid arthritis, hemolytic anemia, hepatic disease, hyperparathyroidism, Paget’s disease, renal failure; (4) use of drugs: replacement weight—thyroxin, glucocorticoids, estrogens or progestagens, diphenylhydantoin, captopril and thiazides, oligoelements (zinc, magnesium) and that meet the following inclusion approaches: (1) consent of the patient to participate in the study; (2) cease of the spontaneous menstruation of at least 1 year of evolution; (3) osteoporosis evidenced by BMD; (4) women with appropriate bone mass. After the selection, in order to collect the information, two instruments of gathering data were designed. First, survey like clinical history included a first part with general data
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and medical dietetic antecedents, and a second part that included general physical exam. In the second instrument, all the obtained information of the analysis of the blood and urine samples was picked up and BMD was made to each subject of study. All patients were extracted with fasting blood for the serum determination of calcium, creatinine, phosphorus, phosphatase alkaline, and analyzed by colorimetric methods. They were also determined for plasma concentration of zinc and of tartrate resistant acid phosphatase (plasmatic isoenzyme 5 of the total phosphatase acid, TRAP), by means of immunoassay, using monoclonal antibodies specifically managed against the bone isoenzyme. The considered standard values of TRAP range 3.8 – 9.9 UI/l. Simultaneously, they were determined in the urine samples of 24 h, creatinine, calcium and zinc. For the determination of the zincuria and the zincemia, the method of atomic absorption spectrometry (AAS), with Shimadzu AA-670 equipment, was used. The equipment was adjusted with a specific lamp of hollow cathode for zinc. Technique sensibility 0.1 ppm (0.01 mg/1000 ml). It was standardized and it optimized the method in a previous work [15], where the results of the zincuria and the zincemia of healthy women pre- and postmenopausal were analyzed. The reference standard values were settled down for the zincuria in 460 – 800 mg/24 h (0.46 – 0.86 ppm) and for the zincemia of 0.9 at 1.4 mg/ml. We concluded that AAS is more sensitive, less expensive and the variety coefficient increases for dilute samples. The zincuria, to the effects of this work, was defined as the concentration of present zinc in a sample of 24 h urine, determined by the method of atomic absorption spectrometry. The reference values for the zincuria in 24 h correspond to 0.46– 0.86 ppm. The zincemia was defined as the concentration of present zinc in a sample of blood whose values oscillate between 0.9 and 1.4 mg/ml, determined by atomic absorption spectrometry. Both groups were practiced with bone mineral densitometry (BMD) through the absorptiometry method for double photon with a Lunar DP3 densimeter, in lumbar column (L2 –L4) in posteroanterior projection and Wards triangle in hip. The results are expressed in grams of hydroxiapatite by unit area (g/cm3), and they are valued according to the densitometric patron of the series of 875 Spaniards (547 women and 328 men), free of chronic disease, without degenerative alterations, and are not taking medicines that could have influenced on the bone mass [16]. These reference values are similar to those obtained in population of white race series (United States, United Kingdom, Australia, Brazil, France) [17,18]. The comparison of the results of the BMD is made with healthy subjects, of the same sex, in the moment when the skeleton presents its biggest maturity, with age understood between 20 and 40 years, and they are evaluated according to a percentage regarding the young population’s BMD and also expressing it in the standard number of deviations that it vary of the values means reached by a population of healthy subjects (Z-score). The value used to determine the appropriate bone mass includes a value for the BMD of 1 standard deviation (S.D.) for under or above the average for young adults. The considered fracture thresholds are the values from inferior BMD to 0.94 g/cm2 for the lumbar column in PA projection and inferior to 0.65 g/cm2 for the femoral neck [19,20]. Also, it considered osteoporosis like a dysfunction in which a decrease of the bone mass exists without a remarkable change in the relationship of mineralized bone and not mineralized bone and that it determines a value of BMD of more than 2.5 standard deviation (S.D.) below the average for a young adult, according to the recommendations of WHO.
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3. Analysis of data The results of this study are presented in the tables with the population’s homogeneous properties, the mean values and the typical deviations for the total of subjects, according to the studied properties. The differences between measures were calculated using Student’s t-test. In the studied variables, the ratio of crossed products to determine the strength of the association were calculated. Also, it was determined for the sensibility, defined as the probability of obtaining a positive result in patients with the disease, or the relation of patients with the disease whose test is positive [21], and the specificity, defined as the probability of obtaining a negative test in individuals without the disease, or the relation of patients that do not have the dysfunction whose test is negative. Simultaneously, the limit of trust to establish the clinical association of the test were determined. The ratio of positive and negative verisimilitude was also determined and it expresses the possibilities that the result of the test happens in a patient with the disease, in comparison with those without the disease, with a trust interval of 95%.
4. Results The age properties, sex, type and time of the ceasing of the menstruation and anthropometrical data (BMI) are presented in Table 1; such results are expressed in percentages, median and standard deviation. With base in the homogeneity of the characteristics described in the Table 1 and by virtue of nonexisting significant differences between the serum and urinary parameters (Table 2 in the population of study), we decided to undertake the study between groups A (postmenopausal osteoporotic women) and B (postmenopausal women with appropriate bone mass) to evaluate the variables object of the present research. The body mass index (BMI) does not evidence significant differences between both groups, although group A presents a greater BMI. The serum calcium in both groups was observed among normal values (8 – 10.2 mg/dl), without significant variation between both groups. The alkaline phosphatase varied from 77 to 155 UI/l (VN: 45 –115 UI/l), with an Table 1 Population’s general characteristics Characteristic
Condition
Value
Patients Sex Age Menstruation cease Spontaneous Surgical Alcoholic habit Associated diseases (exclusion criteria) Drug abuse (exclusion criteria) Body mass index
62 patients Female 52.323 > 3 years 58 patients 4 patients Not present Not present Not present 27.04 kg/m2
100% 100% 52.323 F 6.47 (mean F S.D.) 100% 93.55% 6.45% 100% 100% 100% 27.04 F 3.02 (mean F S.D.)
Source: Data were obtained from survey recollected from each patient.
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Table 2 Studied population’s properties: mean values and standard deviation Characteristic
Group A (mean F S.D.)
Group B (mean F S.D.)
p
Number BMI (kg/m2) Age (years) Serum calcium (mg/dl) Alkaline phosphatase (UI/l) Seric phosphorus (mg/dl) Calciurea (mg/24 h)
32 27.03 51.344 F 7.29 9.013 F 0.869 104 F 22.6 2.7 F 1.3 155.9 F 70.19
30 26.02 50.16 F 4.68 9.410 F 0.627 99.23 F 25.01 2.5 F 0.4 148.08 F 82.98
0.18 (ns) 0.20 (ns) 0.05 (ns) 0.24 (ns) 0.4 (ns) 0.69 (ns)
Source: Data were obtained from survey recollected from each patient. BMI: body mass index; ns = not significant.
average of 104 in group A and 99.233 in group B. The serum phosphorus and the calciuria did not show significant differences between both groups. The mean values of tartrate resistant acid phosphatase (TRAP) were higher in group A (VN: 3.8 –9.9 UI/l), i.e. 9,7391,091 in comparison with group B (Table 3). The BMD values obtained in group B were above the fracture threshold, as much in lumbar column as in the femoral neck, contrary to the finding of group A, in which statistical averages were evidenced so much inside the threshold of fracture risk in their absolute values as in their averages and standard deviation, data corroborated with the Z-score. Obtaining these results, which evidence significant differences between both groups, it is possible to establish the comparison of the two groups measuring the zincemia and the zincuria (Table 4). The average of zinc excretion in absolute values, corrected by creatinine excretion in the group of the postmenopausal women (group A), was significantly above the average of group B (Table 4). Similar data were obtained when measuring the zincemia. When determining the p value between both groups, the results evidence clear differences between them. The ratio of crossed products for the zincuria was 48.6 and for the zincemia was 50. It is high, which demonstrates that a clear association exists between the hyperzincuria and hyperzincemia conditions with the osteoporosis. Based on the effects of this study, it considered the DPA BMD test as gold standard for the diagnosis of osteoporosis, which allowed to use the results of the zinc in urine of 24 h of both groups to establish the Table 3 Comparison between groups A and B for serum method (TRAP) and BMD Characteristic
Group A (mean F S.D.)
Group B (mean F S.D.)
p
TRAP (UI/L) Lumbar column L2 – L4 (g/cm2) Lumbar column L2 – L4 (%) Z-score Wards triangle (g/cm2) Wards triangle (%) Z-score
9.73 F 1.09 0.90 F 15 76.09 F 13.96 2.5 F 0.6 0.650 F 0.194 77.66 F 17.08 2.6 F 0.6
5.26 F 1.29 1.12 F 0.14 99.32 F 7.664 + 1.0 F 1.2 0.933 F 0.083 98.56 F 8.80 + 1.1 F 1.2
0.0001 0.0001 0.0001 0.0001 0.0001 0.0001 0.0001
Source: Data were obtained from survey recollected from each patient. TRAP: tartrate resistant acid phosphatase; ns = not significant; BMD: bone mineral density.
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Table 4 Comparison between zincemia and zincuria Characteristic
Group A (mean F S.D.)
Group B (mean F S.D.)
t
p
Number Zincemia (mg/dl) Creatinine (mg/24 h) Zincuria (mg/creatinine/24 h)
32 2.13 F 0.41 71.21 F 11.56 427.44 F 88
30 1.44 F 0.42 83.98 F 12.74 279 F 83
6.223 4.137 6.796
0.001 0.005 0.001
Source: Data were obtained from survey recollected from each patient.
positive and negative true cases and the positive and negative false cases; the statistical program Medical was used to calculate the sensibility, specificity and verisimilitude ratio. 4.1. Sensibility –specificity and verisimilitude value of zincuria Sensibility = 87.5% Specificity = 73.3% Trust interval CI 95% (71.0 – 96.4) Trust Interval CI 95% (54.1 – 87.7) Prevalence = 0.51 Ratio of positive verisimilitude = 3.28 with a value cohort point diagnose for the test of 336 mg of zinc in 24 h urine Ratio of negative verisimilitude = 0.17 The sensibility of the zincuria test was of 87.5%, with a specificity of 73.35%, using an interval of trust of 95%. The ratio of obtained positive verisimilitude was 3.28 with a value diagnostic cohort point of 336 mg/creatinine in 24 h urine, which denotes the possibility that a woman present osteoporosis every 3.28 times that a subject has zincuria values of 336 mg/mg in creatinine of 24 h urine. The ratio of obtained negative verisimilitude is as low as 0.17. 4.2. Sensibility –specificity and ratio of verisimilitude of the zincemia Sensibility = 93.8% CI 95% (79.2 –99.1) Specificity = 73.3% CI 95%(54.1 –87.7) Prevalence = 0.51 Ratio of positive verisimilitude = 3.52 with a value diagnostic cohort point of 1.6 mg of blood zinc Ratio of negative verisimilitude = 0.08 The sensibility of the zincemia test was of 93.8%, with a specificity of 73.35%, using a trust interval of 95%. The prevalence of recorded osteoporosis in the population of study was 0.51. The ratio of obtained positive verisimilitude was 3.52 with a value diagnostic point cohort of 1.6 mg of zinc in plasma, which suggests the possibility to suffer osteoporosis every 3.52 times that a subject has zincemia values of 1.6 mg of blood zinc when comparing them with a postmenopausal woman with appropriate bone mass. The
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Table 5 Pointers of predictive accuracy of the test Test
Prevalence
Sensibility (95% TI)
Specificity (95% TI)
PV+ (95% TI)
PV
Zincuria Zincemia
0.51 0.51
87.5% (71 – 96.4) 93.8%(79.2 – 99.1)
73.3% (54.1 – 87.7) 73.3% (54.1 – 87.7)
3.28 3.52
0.17 0.08
(95% TI)
The value of diagnostic cohort point for zincuria was 336 mg in 24 h urine. The value of diagnostic cohort point for zincemia was 1.6 mg in blood. TI = trust interval; PV + = reason of positive verisimilitude; PV = reason of negative verisimilitude.
ratio of obtained negative verisimilitude is 0.08, which indicates that a woman has the possibility to have the disease every 0.08 times that the zincemia is high (Table 5).
5. Discussion Osteoporosis is a chronic, complex and multifactorial disease that it can progress slowly per decade until the characteristic bone fractures appear in life. Because there are no symptoms until the fractures happen, few patients are diagnosed on time with the purpose of including them in an effective therapy. This disease has a high incidence in women, due to the accelerated loss of bone that begins when the ovarian function diminishes with the climaterium and it continues for several years after the menopause. In our series, starting from a susceptible population of osteoporosis with a common property, the postmenopausal status, a group of postmenopausal women was compared (n = 32), most with more than 5 years from the last menstrual bleeding, without associated chronic disease neither oligoelements consumption, with osteoporosis evidenced by BMD and determination of blood TRAP (group A), with a group of postmenopausal women likewise (n = 30), with appropriate bone mass determined by BMD and TRAP in normal borders (group B) to evaluate the behavior of the blood zinc concentration and the zinc excretion in 24 h urine. The findings evidence significant differences between both groups when they were compared through typically reliable osteoporosis parameters, as the tartrate resistant acid phosphatase in blood and the BMD in lumbar column (L2 –L4) and Wards triangle. In both cases, the p values ( p < 0.0001) were broadly significant (Table 5). The bone densimetry is a bloodless method of quantitative evaluation of the whole bone mass for the diagnosis of osteoporosis. According to approach of the World Health Organization (WHO), value inferior to 2.5 standard deviations of the standard value are indicative of osteoporosis. The tartrate resistant acid phosphatase as biochemical marker of bone reabsorption can predict the change in the oseum mineral density [22]. Also, it can provide a hint for the risk of fracture. Lindsay [23] of the Helen Hayer Hospital of New York concluded that the biochemical markers could not replace the bone densimetry in series, with the purpose of obtaining a precise determination of the change in the bone mass in the majority of the most outstanding areas. When group A was compared using the zincemia and the zincuria with group B, a p value < 0.0001 was obtained which was widely significant. The determination of the zincemia in group A is ostensibly greater (mean F S.D. = 2.13 F 0.41) when comparing it
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with group B (mean F S.D. = 1.44 F 0.42) with a t value of 6.223 and a p value < 0.0001. These findings agree with those established by Lucena et al. [24], who measured the concentrations of zinc and copper and the relationship that it exists between both elements, in women’s serum samples classified in groups A (women with appropriate bone mass) and B (women with osteoporosis), following selection approaches. This work unit showed that significant evidences existed among the groups of analyzed women and it allowed them to infer that the relationship copper/zinc is a relevant factor in the osteoporosis studies. Our findings when comparing the zincemia among the groups of study are contrary to the results obtained by Are´valo, et al. [25] and Kotkowiak [26], who carried out a comparative study of the relationship zinc/creatinine in pre- and postmenopausal women with osteoporosis and with appropriate bone mass, with and without hormonal replacement therapy in a selected sample of 100 women according to inclusion approaches. The zinc concentrations in serum and urine were determined by atomic absorption spectrometry. The applied statistical analysis showed that did not exist significant differences among the five units analyzed for the averages of the serum zinc concentration. When comparing the zincuria among the groups of study, the t and p values evidence significant differences, results that agree with those obtained by other authors. Are´valo et al. [25] when comparing women with appropriate bone mass and osteoporotical women evidenced that the relationship urinary zinc/creatinine exhibited significant statistical differences among the groups of study. These results equally agree with those obtained in other studies such as Ferna´ndez et al. [27], Herzberg et al. [28] and Relea et al. [29], whom in a study with osteoporotical women determined that most postmenopausal patients had an increase in the urinary zinc excretion and concluded that a woman that has an urinary zinc excretion greater than 800 mg / in 24 h creatinine urine, has near 90% of probability of suffering from osteoporosis. Similar results obtained Szathmari, et al. [30]. Moreover, a study carried out by Herzberg, Lusky, Blonder and Frenkel showed that the urinary zinc excretion not only happens in women with established osteoporosis, but also in healthy women in the early menopause, so the high zinc loss is reflective of the current rate of accelerated bone replacement, before the values of bone mineral density arrive at osteoporosis levels [31]. The discrepancy tests (ratio of crossed products), carried out to determine the association between zincemia and osteoporosis and zincuria and osteoporosis, suggest a good association between the osteoporosis condition and the hyperzincuria and hyperzincemia. The sensibility or relation of patients with osteoporosis whose zincuria is in high range was 87.5% and the specificity of the test was 73.3% with a trust interval of 95%. These results agree with the previous studies [27] in which the sensibility obtained for the zincuria was 66% and the specificity 80%. The ratio of positive verisimilitude made to the zincuria was 3.28 with a diagnostic cohort point value 360 mg/g of creatinine in urine of 24 h. That is to say that a woman who has a zincuria value of 360 mg/creatinine in 24 h urine has a possibility of 87.5% to suffer from osteoporosis every 3.28 times that it is compared that postmenopausal woman with appropriate bone mass. These findings are correlated with those obtained by Herzberg et al. [29]. When comparing the zincemia among the groups of study, the t and p values evidence broadly significant differences, results that agree with those obtained by other authors. The ratio of positive verisimilitude with an interval of 95% indicates the possibility that a
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woman with zincemia superior or equal at 1.6 mg has a possibility of 93.8% to have osteoporosis. The ratio of negative verisimilitude is quite low, 0.08, which agrees with the obtained findings. Most of the biochemical markers of bone replacement were normal in patients with osteoporosis; this can be due to the fact that this disease is a condition where only subtle modifications in the activity of the bone remodeling can take to substantial losses of the bone mass after a long period of time. It is necessary to have in mind that an isolated determination of some blood or urine marker is hardly a small reflection of the active and complicated bone metabolism and that it could be influenced, among other variables, for the degree of bone replacement at the moment of taking the specimen. It is necessary to consider that the results obtained in this study come from a relatively small sample, if we take in consideration the percentage of our women population that are at risk of suffering the disease. Also, it is a prevalence study with a managed sample to a highly susceptible population of postmenopausal osteoporosis (51%), obtained in a single hospital center that possibly does not represent the total of our heterogeneous population’s properties, a reason for which move studies are suggested with a greater population and, in several centers, to be able to extrapolate these results to the general population simultaneously. 6. Conclusions It is clear that a relationship exists among the excretion of zinc in 24 h urine and the appearance of osteoporosis, and the urinary zinc/creatinine relationship is a factor to take in mind in the osteoporosis studies. Judging by our results, the zincuria seems to be associated to osteoporosis. The zincemia as biochemical indicator of osteoporosis seems to be highly efficient. The indicators of discrepancy and accuracy of the zincemia and the zincuria are highly indicative of the value of these parameters as biochemical markers of bone reabsorption for the diagnosis of osteoporosis. Although it is certain that the biochemical markers cannot replace the bone densimetry in series, with the purpose of obtaining a precise determination of the change in the bone mass in the majority of the most outstanding areas, nowadays, they are very interesting as the biochemical markers of reabsorption, by virtue of their use to evaluate the activity of the disease, their rate of bone loss, and as indispensable tool in the pursuit from the answer to the treatment of this disease. References [1] Consensus development conference: diagnosis, prophylaxis, and treatment of osteoporosis, Am. J. Med. 94 (1993) 646 – 650. [2] S. Krane, M. Holick, Metabolic bone disease, Osteoporosis, in: K.J. Isselbacher, E. Braunwald, J.D. Wilson, A.S. Fauci, D.L. Kasper (Eds.), Harrison’s Principles of Internal Medicine, 13th edn., McGraw-Hill, New York, 1994, pp. 72 – 84. [3] K. Lyles, Osteoporosis en el anciano, in: W. Kelley (Ed.), Medicina Interna, Panamericana, Buenos Aires, 1993, pp. 2624 – 2631. [4] B.L. Riggs, J. Melton, Involutional osteoporosis, N. Engl. J. Med. 314 (1986) 1676 – 1686. [5] Ch. Lambing, Osteoporosis prevention, detection, and treatment, Post Grad. Med. 107 (7) (2000) 37 – 56.
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