Bone Mineral Density of the Spine and Femur in Healthy Saudi

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Calcif Tissue Int (1999) 65:2328



                                                                                                                       1999 Springer-Verlag New York Inc.




Bone Mineral Density of the Spine and Femur in Healthy Saudi
Females: Relation to Vitamin D Status, Pregnancy, and Lactation
N. N. Ghannam,1 M. M. Hammami,1 S. M. Bakheet,2 B. A. Khan3
1
  Department of Medicine (MBC-46), King Faisal Specialist Hospital and Research Centre, PO Box 3354, Riyadh 11211, Saudi Arabia
2
  Department of Radiology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
3
  Department of Biomedical Statistics and Scientific Computing, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia

Received: 21 July 1998 / Accepted: 1 November 1998


Abstract. Bone mineral density (BMD) measurements of                         influenced by genetic, environmental, and hormonal factors
the anterio-posterior lumbar spine and the proximal femur                    [5]. Ethnic and racial variations of bone density are there-
using dual-energy x-ray absorptiometry, as well as relevant                  fore expected [615].
clinical and biochemical parameters, were determined in                          Vitamin D deficiency, an established risk factor for de-
321 healthy Saudi females in order to establish reference                    creased bone mass, is common in Saudi Arabia [16]. Fur-
values and to study the effects of physical and lifestyle                    thermore, the high rate of pregnancy and longer duration of
factors on BMD. Mean  SD of age, body mass index                            breast feeding in Saudi females compared with western fe-
(BMI), number of pregnancies, and total duration of lacta-                   males may affect calcium balance and bone density [1721].
tion were 35.4  11.3 years, 26.5  5.2 kg/m2, 3.1  3.1, and                    The aims of the study were to (1) establish normative
23.7  42.4 months, respectively. Mean  SD of serum                         data for bone mineral density (BMD) at the anterio-
calcium, 25-hydroxyvitamin D (25OHD), and PTH levels                         posterior lumbar spine and femur in Saudi females using
were 2.37  0.09 mmol/liter, 24.5  17.2 nmol/liter, and                     dual x-ray absorptiometry (DXA), (2) compare BMD of
52.0  30.8 pg/ml, respectively. Peak BMD values were                        Saudi females and their USA counterparts, and (3) examine
observed around age 35 years at the spine and earlier at the                 the relationship of BMD to vitamin D status, pregnancy, and
femur. Compared with USA females, Saudi females had                          lactation.
lower weight-matched Z scores at the spine (-0.126 
1.078, P  0.04), femoral neck (-0.234  0.846, P <
0.0001), and Ward's triangle (-0.269  1.015, P < 0.0001).                   Materials and Method
Further, the prevalence of osteopenia and osteoporosis in
subjects 31 years old were 1841% and 07%, respec-                          Subjects
tively, depending on the site examined. Severe hypovita-
minosis D (25OHD level 20 nmol/liter) was present in                         Three hundreds and twenty-one healthy Saudi female volunteers
52% of the subjects. However, there was no correlation                       were recruited from the city of Riyadh, Saudi Arabia through
between 25OHD level and BMD at any site. Parathyroid                         advertisements in local newspapers and local hospitals. Informed
hormone (PTH) levels correlated significantly with 25OHD                     consent was obtained from all subjects (or their parents), and the
                                                                             study was approved by the Research Advisory council, King Faisal
levels (r  -0.28, P < 0.0001) and with weight-matched                        Specialist Hospital and Research Centre. A questionnaire includ-
BMD Z scores at the spine (r  -0.17, P  0.005), femoral                      ing age, age at menarche, age at menopause, number of pregnan-
neck (r  -0.16, P  0.007), and Ward's triangle (r                            cies, months of lactation, smoking, alcohol intake, medical history,
-0.2, P  0.0008), suggesting that the distribution of                        and drugs, was obtained from all volunteers. Subjects who had a
25OHD levels in the cohort is below the threshold needed                     medical illness or were on drugs known to interfere with calcium
for maintaining normal BMD. On the other hand, number of                     metabolism were excluded from the study. All subjects were am-
pregnancies and total duration of lactation correlated with                  bulatory and none was pregnant or had a history of fracture. Sub-
weight-matched BMD Z scores at the spine (r  -0.17, P                        jects were weighed on an electric scale wearing minimal clothing.
 0.003; r  -0.1, P  0.08, respectively). We conclude                         Height was measured to the nearest centimeter using a stadiometer.
                                                                             Body mass index (BMI) was calculated as weight (kg)/height (m)2.
that BMD in healthy Saudi females is significantly lower                     Blood was drawn in the fasting state to determine serum calcium
than in their USA counterparts. This may be due in part to                   and calcitropic hormones levels. The blood was drawn on recruit-
increased number of pregnancies and longer duration of                       ment which occurred over all four seasons of the year.
lactation together with prevalent vitamin D deficiency.

                                                                             Bone Mineral Density Measurements

Osteoporosis, a major health problem worldwide [1, 2], is                    BMD measurements were determined at the lumbar spine (L2L4)
characterized by low bone mass and microarchitectural de-                    anterio-posteriorly and at the left femoral neck, Ward's triangle,
terioration of bone structure [3, 4]. Bone mass is determined                and trochanter using DXA with DPX Version 3.6 scanner (Lunar
by peak bone mass and the rate of bone loss; both are in turn                Corp., Madison, WI) according to the manufacturer's operator
                                                                             manual. All measurements were performed at the Section of
                                                                             Nuclear Medicine, King Faisal Specialist Hospital and Research
                                                                             Centre by one of two experienced technologists and reviewed by a
Correspondence to: M. M. Hammami                                             nuclear medicine physician. The calibration of the absorptiometer
24                                                                                              N. N. Ghannam et al.: BMD in Saudi Females

Table 1. Clinical and biochemical characteristicsa of 321 healthy Saudi females
Age                           S Ca                 25OHD              PTH                Pregnancy          BMI               Lactation
(year)         Number         (mmol/liter)         (nmol/liter)       (pg/ml)            (number)           (kg/m2)           (month)
1020           29            2.39  0.06          26.5  26.9        44.0  23.5        --                 21.8  3.4        --
2130           91            2.36  0.1           22.8  15.6        45.5  25.4        1.2  1.6          24.6  4.5          6.8  12.5
3140           98            2.35  0.09          24.1  15.6        55.9  32          3.8  2.7          26.8  4.1        26.4  36
4150           71            2.37  0.09          24.7  16.2        55.8  36.9        4.6  2.9          28.8  5.5        31.9  40.4
>50             32            2.42  0.06          28.6  18.3        56.3  28.7        6  3.9            30.8  5.8        72.4  84.3
Total          321            2.37  0.09          24.5  17.2        52.0  30.8        3.1  3.1          26.5  5.2        23.7  42.4
a
    Mean  SD. S Ca, serum calcium; 25OHD, 25-hydroxyvitamin D; BMI, body mass index



Table 2. BMDa of lumbar spine and femur of 321 healthy Saudi females
Age (year)       L2L4               Femoral neck        Ward's triangle        Trochanter
1020            1.130  0.113       0.981  0.104       0.931  0.145          0.808  0.115
2130            1.145  1.161       0.930  0.12        0.884  0.149          0.765  0.112
3140            1.181  0.131       0.937  0.119       0.847  0.137          0.784  0.114
4150            1.173  0.162       0.947  0.112       0.832  0.125          0.800  0.117
>50              0.997  0.243       0.857  0.117       0.742  0.164          0.761  0.129
Total            1.145  0.167       0.933  0.119       0.851  0.148          0.782  0.116
a
    Mean  SD (g/cm2)



was checked daily. The results of the measurements were ex-              Results
pressed in g/cm2. Lunar USA normal database supplied by the
manufacturer was used to derive Z scores (matched for age and            Three hundred and twenty-one healthy Saudi females were
weight) and T scores (reference age 2045 years).                        recruited for the study. All had normal serum calcium and
                                                                         phosphate levels. Two percent of the subjects had mildly
                                                                         elevated alkaline phosphatase levels. Mean alkaline phos-
Biochemical and Hormonal Measurements                                    phatase and albumin levels were 72.7  32.9 U/liter and
                                                                         40.7  2.4 g/liter, respectively. The mean  SD of height
Intact PTH level was determined by a two-site immunoradiometric          and weight were 158.1  6.2 cm and 66.4  13.0 kg, re-
assay (Intact PTH, Nichols Institute Diagnostics, San Juan Cap-          spectively. The cohort was divided into five age groups. The
istrano, CA.). The normal range intraassay and interassay variation      relevant clinical and biochemical characteristics of each age
supplied by the manufacturer are 1065 pg/ml, 1.83.4%, and              group are shown in Table 1.
5.66.1%, respectively. 25OHD level was determined by radioim-
munoassay (Nichols Institute Diagnostics, San Juan Capistrano,
CA). The normal range, intraassay, and interassay variation sup-         Bone Mineral Density of the Lumbar Spine and Femur
plied by the manufacturer are 1674 ng/ml, 8.110.2%, and 10.9
15%, respectively. The subjects were divided according to their          Table 2 summarizes BMD at the anterio-posterior lumbar
serum 25-hydroxyvitamin D levels [22] into those with severe             spine (L2L4) and three sites of the femur. Peak BMD at the
hypovitaminosis D (25OHD level 20 nmol/liter) and those with             lumbar spine was seen in the 3140 year age group. BMD
moderate hypovitaminosis D or adequate vitamin D stores                  at Ward's triangle had an apparent peak in the 1020 year
(25OHD level >20 nmol/liter). All hormonal and biochemical
measure-ments were performed in the clinical laboratory at King          age group. For BMD at femoral neck and trochanter, there
Faisal Specialist Hospital and Research Centre.                          were two apparent peaks--one in the 1020 year age group
                                                                         and one in the 4150 year group.
                                                                             BMD values of the femoral neck and trochanter in the
                                                                         1020 year group had normal distribution with minimum,
Statistical Analysis                                                     median, and maximum values of 0.783, 0.998, and 1.232
                                                                         g/cm 2 (femoral neck) and 0.583, 0.807, and 1.038
Data were analyzed using JMP version 3.1 (SAS Institute, Cary,           g/cm2trochanter). The corresponding values in the next age
NC). Values were expressed as mean  standard deviation (SD).            group (2130 years) were 0.686, 0.926, and 1.257 g/cm2
To test if BMD of healthy Saudi females is different from BMD of
USA healthy females, Z scores of Saudi females (derived using            (femoral neck) and 0.530, 0.766, and 1.068 g/cm2 (trochan-
USA normal database) were compared with zero using the t-test.           ter) which also had normal distribution. The means of the
The percentage of individuals with osteopenia or osteoporosis            two groups were statistically different for both femur neck
were calculated according to World Health Organization (WHO)             and trochanter.
criteria [23]. Correlation was measured by Pearson's correlation
coefficient. Linear and polynomial regression were used to calcu-
late the best curve fit for BMD versus age and BMI. The two-tailed       Comparison of BMD in Healthy Saudi Females and Their
t-test was used to compare BMD in the subgroup with severe               USA Counterparts
hypovitaminosis D with the rest of the cohort. Differences were
considered statistically significant at P < 0.05.                        Table 3 shows BMD T and Z scores of healthy Saudi fe-
     N. N. Ghannam et al.: BMD in Saudi Females                                                                                                                                                                                                                        25




                                                                           0.210  1.465
                                                                          -0.132  0.917
                                                                          -0.099  0.933
                                                                          -0.035  0.926
                                                                          -0.006  0.929
                                                                          -0.057  0.978
                                                                                                                                                                                                             males using healthy USA females as controls. The preva-
                                                                                                                                                                                                             lence of osteopenia (T score lower than -1 SD) and osteo-
                                                             Trochanter
                                                                                                                                                                                                             porosis (T score lower than -2.5 SD) in healthy Saudi fe-
                                                                                                                                                                                                             males, according to age group, are summarized in Table 4.
                                                                                                                                                                                                                 Z scores were significantly lower than zero (using two-
                                                                                                                                                                                                             tailed t-test) for the whole cohort at the lumbar spine (P 
                                                                                                                                                                                                             0.04), femoral neck (P < 0.0001), and Ward's triangle (P <
                                                                                                                                                                                                             0.0001). Z scores were also significantly lower than zero at
                                                                                                                                                                                                             the femoral neck (P < 0.0001) and Ward's triangle (P 
                                                                          -0.290  1.362
                                                                          -0.233  1.063
                                                                          -0.358  0.967
                                                                          -0.239  0.887
                                                                          -0.192  0.999
                                                                          -0.269  1.015                                                                                                                     0.04) for 2130 year age group; femoral neck (P  0.0009)
                                                                                                                                                                                                             and Ward's triangle (P  0.0005) for 3140 year age
                                                                                                                                                                                                             group; and at Ward's triangle (P  0.03) for 4150 year age
                                                             Ward




                                                                                                                                                                                                             group. However, in the 1020 year age group, Z scores were
                                                                                                                                                                                                             significantly higher than zero at the lumbar spine (P <
                                                                                                                                                                                                             0.0001) and femoral neck (P  0.006). The later observa-
                                                                                                                                                                                                             tion could not be explained by an earlier age of menarche in
                                                                                                                                                                                                             Saudi compared with USA females as the mean  SD age of
                                                                           0.274  0.462
                                                                          -0.397  0.891
                                                                          -0.309  0.876
                                                                          -0.117  0.841
                                                                          -0.216  0.716
                                                                          -0.234  0.846




                                                                                                                                                                                                             menarche in Saudi females was 12.8  1.64 years.
                                                             Neck




                                                                                                                                                                                                             Correlation of BMD with Clinical and Biochemical Parameters
                                                                                           Mean  SD (compared to USA females). The reference age for T scores is 20-45 years. Z scores are weight-matched




                                                                                                                                                                                                             There were linear correlations between age and BMD at the
                                                                                                                                                                                                             spine and femur and polynomial correlations between BMI
                                                                           0.551  0.601
                                                                          -0.188  0.926
                                                                          -0.102  0.966
                                                                          -0.159  1.315
                                                                          -0.484  1.336
                                                                          -0.126  1.078




                                                                                                                                                                                                             and BMD at the spine and femur (Table 5). Height was also
                                                                                                                                                                                                             correlated positively with BMD at the spine (r  0.17, P 
                                                                                                                                                                                                             0.003), femoral neck (r  0.23, P < 0.0001), and Ward's
                                                             L2L4




                                                                                                                                                                                                             triangle (r  0.19, P  0.0005).
                                                                                                                                                                                                                 As shown in Table 6, number of pregnancies and total
                                                         Z




                                                                                                                                                                                                             duration of lactation correlated negatively with BMD at the
                                                                                                                                                                                                             spine and Ward's triangle. To examine the association of
                                                                                                                                                                                                             BMD with pregnancy and lactation independently, the co-
                                                                          -0.430  2.415
                                                                          -0.225  1.017
                                                                          -0.050  1.034
                                                                           0.102  1.060
                                                                          -0.261  1.171
                                                                          -0.099  1.105




                                                                                                                                                                                                             hort was divided into those with 3 pregnancies (59%) or
                                                             Trochanter




                                                                                                                                                                                                             >3 pregnancies (41%) and those with total duration of lac-
                                                                                                                                                                                                             tation of 5 months (51%) or >5 months (49%). In the
                                                                                                                                                                                                             subgroup with >3 pregnancies, total duration of lactation
                                                                                                                                                                                                             correlated with BMD at the spine (r  -0.28, P  0.003).
                                                                                                                                                                                                             On the other hand, number of pregnancies correlated with
                                                                                                                                                                                                             BMD at Ward's triangle (r  -0.21, P  0.01) in the
                                                                                                                                                                                                             subgroup with 5 pregnancies and with BMD at the spine
                                                                           0.560  1.207
                                                                          -0.198  1.148
                                                                          -0.490  1.050
                                                                          -0.603  0.960
                                                                          -1.298  1.258
                                                                          -0.493  1.134




                                                                                                                                                                                                             (r  -0.3, P  0.0003) in the subgroup with >5 pregnan-
                                                                                                                                                                                                             cies. Furthermore, there was a negative correlation between
                                                                                                                                                                                                             BMD Z scores at the spine and number of pregnancies (r 
                                                                                                                                                                                                             -0.17, P  0.003) and duration of lactation (r  -0.1, P 
                                                             Ward
Table 3. BMD T and Z scoresa of lumbar spine and femur




                                                                                                                                                                                                             0.08). The correlation of BMD with the number of preg-
                                                                                                                                                                                                             nancies was further examined in each age group. Number of
                                                                                                                                                                                                             pregnancies correlated with BMD at the spine (r  -0.55,
                                                                                                                                                                                                             P  0.002), femoral neck (r  -0.39, P  0.03), Ward's
                                                                           0.283  0.856
                                                                          -0.420  0.996
                                                                          -0.357  0.992
                                                                          -0.284  0.916
                                                                          -1.024  0.972
                                                                          -0.421  0.993




                                                                                                                                                                                                             triangle (r  -0.45, P  0.02), and trochanter (r  -0.36,
                                                                                                                                                                                                             P  0.05) in the age group >50 years. The correlation
                                                                                                                                                                                                             between the number of pregnancies and BMD was not sig-
                                                             Neck




                                                                                                                                                                                                             nificant in other age groups.
                                                                                                                                                                                                                 PTH level correlated significantly with BMD at the
                                                                                                                                                                                                             spine, femoral neck, and Ward's triangle (Table 6). Since
                                                                                                                                                                                                             there was positive correlation between PTH level and age (r
                                                                                                                                                                                                              0.13, P  0.02), we also examined the relation of PTH
                                                                          -0.031  0.843
                                                                          -0.364  0.985
                                                                          -0.128  1.020
                                                                          -0.228  1.349
                                                                          -1.447  1.590
                                                                          -0.368  1.223




                                                                                                                                                                                                             levels to BMD Z scores. PTH levels correlated with BMD
                                                                                                                                                                                                             Z scores at the spine (r  -0.17, P  0.005), femoral neck
                                                                                                                                                                                                             (r  -0.16, P  0.007), Ward's triangle (r  -0.2, P 
                                                             L2L4




                                                                                                                                                                                                             0.0008), and trochanter (r  -0.11, P  0.06).
                                                                                                                                                                                                                 25-Hydroxyvitamin D levels correlated with serum
                                                         T




                                                                                                                                                                                                             calcium (r  0.23, P  0.0001), alkaline phosphatase
                                                                                                                                                                                                             (r  -0.14, P  0.02), and PTH (r  -0.28, P < 0.0001)
                                                                                                                                                                                                             levels, and BMI (r  -0.12, P  0.04). However, 25-
                                                                          1020
                                                                          2130
                                                                          3140
                                                                          4150
                                                         years




                                                                          Total




                                                                                                                                                                                                             hydroxyvitamin D level did not correlate significantly with
                                                         Age




                                                                          >50




                                                                                                                                                                                                             BMD (or BMD Z scores) at any of the sites examined. The
                                                                                           a
26                                                                                                N. N. Ghannam et al.: BMD in Saudi Females

Table 4. Prevalence (%) of osteopenia and osteoporosis in 321 healthy Saudi females
                            L2L4     Femoral neck         Ward's triangle         Trochanter
Age 3140 (98)
  T < - 1 SD                19        27                   38                      18
  T < - 2.5 SD               1         2                    3.2                     0
Age 4150 (71)
  T < - 1 SD                24        23                   38                      16
  T < -2.5 SD                5.6       1.4                  5.9                     0
Age > 50 (32)
  T < - 1 SD                66        47                   59                      22
  T < - 2.5 SD              28         6                   19                       0
Total (201)
  T < - 1 SD                27        29                   41                      18
  T < - 2.5 SD               7         2.5                  5.1                     0
The number of subjects in each group is shown in parenthesis
T  T-score



Table 5. Regression of BMD on BMI and age in 321 healthy Saudi females
                 BMI                            Age
                 Best fit             P value Best fit                                  P value
                                                                               2
L2L4            1.075 + 0.0026 BMI 0.14    0.820 + 0.0216 age - 0.0003 age   <0.0001
Femoral neck     0.775 + 0.0059 BMI <0.0001 0.879 + 0.0052 age - 0.00009 age2 0.0004
Ward's
  Triangle       0.754 + 0.0037 BMI 0.022 0.896 + 0.0020 age - 0.00008 age2 <0.0001
Trochanter       0.566 + 0.0082 BMI <0.0001 0.706 + 0.0047 age - 0.00007 age2 0.23
BMD (g/cm2); age (year); BMI (body mass index, kg/m2)



Table 6. Correlationa of BMD with clinical and biochemical parameters in 321 healthy Saudi
females
                   L2L4             Femoral neck         Ward's triangle      Trochanter
25OHD               0.03 (0.6)        0.003 (0.96)         0.03 (0.7)           0.04 (0.5)
PTH                -0.14 (0.02)      -0.16 (0.006)        -0.23 (0.0001)       -0.1 (0.08)
Pregnancy          -0.14 (0.02)      -0.1 (0.08)          -0.23 (0.0001)        0.03 (0.6)
Lactation          -0.15 (0.01)      -0.08 (0.17)         -0.17 (0.005)         0.02 (0.7)
a
    Pearson correlation. Numbers in parenthesis are P values


cohort was divided into two groups according to 25-                    Discussion
hydroxyvitamin D level; 52% had severe hypovitaminosis
D. Compared with the rest of the cohort, this group had
lower serum calcium (2.35  0.09 versus 2.38  0.08 mmol/              We have provided a database of BMD at the lumbar spine,
liter, P  0.001), and albumin (40.3  2.4 versus 41.1  2.2            femoral neck, Ward's triangle, and trochanter in healthy
g/liter, P  0.004) levels; and higher PTH (59.0  31.4                 Saudi females aged 1271 years and have made the follow-
versus 44.5  28.6 pg/ml, P  0.0001) and alkaline phos-                ing observations: (1) spine BMD peaks at age 3140 years,
phatase (78.6  41.2 versus 66.8  20.7 U/liter, P  0.002)             whereas femur BMDs have two apparent peaks, one at 10
levels. However, BMD measurements of the spine and three               20 years and one at 4150 years; (2) healthy Saudi females
femur sites were not significantly different between the               have significantly lower BMD at the spine, femoral neck,
two groups. Because the severe hypovitaminosis D group                 and Ward's triangle than age- and weight-matched healthy
was significantly younger (33.9  10.3 versus 36.9  11.2              USA females; (3) the prevalence of osteopenia and osteo-
year, P  0.02), we also compared Z scores of the two                   porosis in otherwise healthy Saudi females over 31 years
groups. The severe hypovitaminosis D group tended to have              old ranged from 18 to 41% and 0 to 7%, respectively, de-
lower Z scores at the spine (-0.18  1 versus -0.003  1.2,            pending on the site examined; (4) although vitamin D de-
P  0.19), femoral neck (-0.28  0.83 versus -0.18  0.86,              ficiency was common in the study population, 25OHD level
P  0.34), Ward's triangle (-0.41  1.0 versus -0.16  1.0,             did not correlate with any of the BMD measurements. How-
P  0.05), and trochanter (-0.16  1.0 versus 0.06  1,                 ever, 25OHD levels as well as several BMD measurements
P  0.07). However, none was statistically significant.                 correlated negatively with PTH levels; and (5) number of
N. N. Ghannam et al.: BMD in Saudi Females                                                                                    27

pregnancies and total duration of lactation correlated nega-      minimum value for vitamin D sufficiency in adults over the
tively with BMD measurements.                                     age of 49 years [31].
    Our study has several limitations. First, the study sample        Several studies have shown that lactation can be associ-
may not be representative of the average healthy Saudi fe-        ated with substantial BMD loss of the lumbar spine and
male. Although we advertised in local newspapers and hos-         femur [18, 19] that is related to changes in parathyroid
pitals, most of the respondents were hospital employees or        hormone-related peptide (PTHrP), estradiol, and prolactin
their relatives. Furthermore, the population of Riyadh, the       levels [32] but not PTH, 25OHD, and 1,25(OHD)2D3 levels
capital of Saudi Arabia, may not be representative of the         [33], and is largely not affected by calcium supplementation
population of Saudi Arabia at large. It is expected that study    [34, 35]. The lactation-associated loss in BMD usually re-
participants may have a more westernized lifestyle with less      covers once lactation is ceased. However, it may take up to
physical activity, calcium intake, and sun exposure, and less     12 and 18 months postparturition, respectively, for the lum-
caloric malnutrition than average. The combined effect of         bar spine and femoral neck BMD to recover [19, 33]. Fur-
these factors on BMD would be difficult to predict. Second,       thermore, it is not clear whether BMD is completely re-
our sample size for ages 1020 years and >50 years is             stored after weaning [34, 36, 37], especially if lactation
relatively small. Third, the study is cross-sectional rather      continues for more than 9 months [19]. The influence of
than longitudinal and the apparent BMD peaks should there-        pregnancy on BMD is still controversial and less well stud-
fore be interpreted with caution.                                 ied [20, 21]. Our cross-sectional study suggests that mul-
    Normative data for BMD in the Saudi (Arab) population         tiple pregnancies may be independently associated with
have not been well established. Two previous studies ex-          lower BMD Z scores at the spine. The relatively higher rate
amined BMD in a healthy Saudi population [15, 24]. One            of pregnancies and longer duration of lactation in Saudi
                                                                  females could account, at least in part, for the lower BMD
study measured BMD at the radius by single photon absorp-         values compared with USA females. This could also explain
tiometry (SPA) [24] and the other BMD at the spine and            the unexpected finding of higher BMD values at the femur
femur by DXA [15]. Neither study determined levels of             in ages 1020 years compared with older age groups (Table
calcium or calcitropic hormones which are of particular im-       2) and lower Z scores at the femur in the reproductive age
portance given the prevalence of hypovitaminosis D in             group compared with younger and older age groups (Table
Saudi Arabia [16]. The potential effects of pregnancy and         3). The latter finding supports the view that the effects of
lactation on BMD [1721] were not studied.                        pregnancy and lactation on BMD are reversible. Neverthe-
    The lower BMD in healthy Saudi females compared with          less, a high yearly incidence of proximal femur fracture of
USA females that was observed in the current and previous         1/1000 Saudi females >50 years old has been reported [38].
[15] studies could not be accounted for by lower body             This, coupled with our observation that the number of preg-
weight, as is the case in other Asian females [8, 9, 13], since   nancies correlated best with BMD at the spine and femur in
we used weight-matched Z scores. We therefore examined            the >50 age group suggest that the recovery from pregnancy
the possible role of vitamin D deficiency. Hypovitaminosis        and lactation-induced changes in BMD may not be com-
D was prevalent in our study population with a mean               plete by the early postmenopausal years.
25OHD level of 24.5  17.2 nmol/liter, confirming previous            In summary, we have provided normative data for BMD
reports [16]. However, we found no correlation between            at the lumbar spine, femoral neck, Ward's triangle, and
25OHD level and BMD at any of the sites examined. More-           trochanter in healthy Saudi females. The observed BMD
over, BMD in the subgroup with severe hypovitaminosis D           values are significantly low compared with USA normative
did not significantly differ from BMD of the rest of the          data which could be due, at least in part, to increased num-
cohort.                                                           ber of pregnancies and longer duration of lactation together
    The fact that 25OHD levels correlated positively with         with prevalent hypovitaminosis D.
serum calcium levels and negatively with alkaline phospha-
tase and PTH levels attests to the physiologic importance of
the observed low 25OHD level and makes the observed lack
                                                                  Acknowledgment. We thank Ms. Najwa A Darar for data manage-
of effect on BMD unexpected [25, 26]. Younger individuals         ment and Ms. Judith Lansi Sosa for expert secretarial help.
in our cohort tended to have lower 25-hydroxyvitamin D
levels suggesting a potential confounding by age. However,
there was also no correlation between 25OHD levels and            References
BMD Z scores. Confirming previous studies [27, 28],
we have found a negative association between 25-
                                                                   1. O'Neill TW, Felsenberg D, Varlow J, Cooper C, Kanis JA,
hydroxyvitamin D levels and BMI, thus, a possible con-                Silman AJ (1996) The prevalence of vertebral deformity in
founding by BMI cannot be excluded. It is also possible that          European men and women: the European vertebral osteopo-
the individual 25OHD levels obtained in the current study             rosis study. J Bone Miner Res 11:10101018
do not accurately reflect the individual long-term mean lev-       2. Cooper C, Campion G, Melton LJ (1992) Hip fractures in the
els, as substantial variation in 25OHD levels due to season-          elderly: a worldwide projection. Osteoporosis Int 2:285289
ality, sunlight exposure, and previous supplementation are         3. Consensus Development Conference (1993) Diagnosis, pro-
expected [2830]. Nevertheless, the most likely explana-              phylaxis and treatment of osteoporosis. Am J Med 94:646
tion of the observed lack of association between 25-                  650
hydroxyvitamin D levels and BMD is that the distribution of        4. Kanis JA, Melton LJ III, Christiansen C, Johnston CC, Khal-
                                                                      taev N (1994) The diagnosis of osteoporosis. J Bone Miner
25OHD levels in the cohort is below the threshold needed              Res 9:11371141
for maintaining normal BMD [25]. This is supported by the          5. Riggs BL, Melton LJ III (1986) Involutional osteoporosis. N
finding that PTH level increases as 25OHD level declines              Engl J Med 314:16761684
below 110122 nmol/liter [28, 30]. In fact, a 25OHD level          6. Lunt M, Felsenberg D, Reeve J, Benevolenskaya L, Cannata J,
of 50 nmol/liter, which is well above the mean level ob-              Dequeker J, Dodenhof C, Falch JA, Masaryk P, Pols HA, Poor
tained in our study, has been recently suggested to be the            G, Reid DM, Scheidt-Nave C, Weber K, Varlow J, Kanis JA,
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