Changes in Bone Mineral Density Following Treatment of Osteomalacia Original Article Bhambri,

Transcription

Journal of Clinical Densitometry, vol. 9, no. 1, 120–127, 2006
Ó Copyright 2006 by The International Society for Clinical Densitometry
1094-6950/06/9:120–127/$32.00
DOI: 10.1016/j.jocd.2005.11.001
Original Article
Changes in Bone Mineral Density Following Treatment
of Osteomalacia
Rajiv Bhambri,1 Vaishali Naik,1 Nidhi Malhotra,1 Shilpa Taneja,1 Saurabh Rastogi,1
Uma Ravishanker,2 and Ambrish Mithal*,1
1
Department of Endocrinology and Diabetes; and 2Department of Nuclear Medicine,
Indraparastha Apollo Hospital, Sarita Vihar, New Delhi, India
Abstract
Osteomalacia is characterized by defective mineralization and low bone mineral density (BMD). Clinical and biochemical improvements typically occur within a few weeks of starting treatment, though the bone mineral deficits
may take longer to correct. We report a case series of 26 patients with frank osteomalacia (pseudo fractures on Xrays, elevated serum total alkaline phosphatase and parathyroid hormone, normal/low serum calcium and phosphorus, and low serum 25-hydroxy vitamin D) who were followed-up for changes in BMD during treatment using dualenergy X-ray absorptiometry (DXA). There were 23 patients with nutritional vitamin D deficiency, 2 with malabsorption syndrome, and 1 with renal tubular acidosis. All patients were treated with vitamin D and calcium; the 3
patients with associated disorders were treated accordingly. At baseline, there was low BMD at all sites tested. The
rate of increase in vertebral and hip BMD was rapid in the initial few months, which subsequently slowed down. In
contrast to the large increases in BMD at the femoral neck and lumbar spine, the radial BMD did not recover. At the
time when most patients had marked clinical and biochemical improvement (2.8 6 1.4 mo), the vertebral and hip
BMD, although improved from baseline, had not completely recovered. Bone loss at the forearm (cortical site)
appears to be largely irreversible. Although the clinical correlates of these changes are presently unclear, BMD
measurements are useful in assessing the initial severity of bone loss as well as the response to therapy.
Key Words: Bone mineral density; hypovitaminosis D; osteomalacia; secondary hyperparathyroidism.
patients respond remarkably well, with gratifying clinical,
biochemical, and radiological recovery. The musculoskeletal
symptoms disappear, abnormalities in serum levels of calcium, phosphorus, and alkaline phosphatase are reversed
and the pseudo fractures heal. However, these parameters
may not be adequate to assess the endpoints of therapy, as
the time course and ultimate extent of recovery in bone mineral deficits at different skeletal sites is not completely
understood.
The BMD measurement by dual-energy X-ray absorptiometry (DXA) as such is not required for diagnosis of osteomalacia. Low BMD seen in osteomalacia reflects the
replacement of mineralized by unmineralized osteoid and
not the reduction of bone matrix. The changes in serial
BMD during treatment of osteomalacia have been used to
Introduction
Osteomalacia is a common metabolic bone disorder in
countries such as India due to suboptimal nutrition (1,2).
They are characterized by defective mineralization resulting
in low bone mineral density (BMD). When treated with adequate vitamin D and calcium, the unmineralized matrix gets
mineralized, resulting in marked increase in BMD. Most
Received 10/22/04; Revised 07/04/05, 10/07/05, 11/29/05;
Accepted 11/29/05.
*Address correspondence to: Ambrish Mithal, MD, DM, Sr. Consultant, Endocrinology and Diabetes, Indraparastha Apollo Hospital,
Sarita Vihar, New Delhi 110044, India. E-mail: ambrishmithal@
rediffmail.com
120
Changes in BMD and Osteomalacia
assess the response to therapy. There is limited data regarding
the changes in BMD during treatment of osteomalacia. In this
article, we report a case series of 26 Asian Indian patients,
both male and female, and adolescents and adults, who
were treated for osteomalacia, and the changes in BMD at
the hip, spine, and forearm were assessed.
121
Statistical Methods
Correlation between various parameters was calculated by
the correlation coefficient. The percent change in a parameter,
at the time Z, was calculated by the following Eq. 1:
value of parameter at time Z2value at baseline
value at baseline
100
ð1Þ
%change 5
Materials and Methods
Subjects
We reviewed the clinical charts of 69 patients with a diagnosis of osteomalacia of any etiology seen in our unit between
1999 and 2002 at Indraprastha Apollo Hospital, New Delhi,
India. Patients with frank osteomalacia based on characteristic clinical and biochemical features, and those who had at
least 2 serial BMD measurements were included in the analysis. The biochemical criteria consisted of raised alkaline
phosphatase (O117 U/L), raised parathyroid hormone
(PTH) (O65 pg/mL), low phosphorus (!2.7 mg/dL), low vitamin D levels (!20 ng/mL), and low or normal calcium
levels (!8.4 mg/dL). Patients with coexisting illnesses that
affect BMD such as thyrotoxicosis, glucocorticoid excess,
and primary hyperparathyroidism were excluded from the
analysis. Twenty-six patients fulfilled these criteria and their
data are presented. There were no controls; this report is on
a series of patients.
Measurements
Patient history, examination, and laboratory and radiographic assessments (including BMD measurements) were
conducted before and during treatment at regular intervals.
None of the patients had bone histomorphometry for the diagnosis of osteomalacia. All patients were treated with vitamin
D (60,000 IU/wk of cholecalciferol) and calcium (between 1–
2 g/d), and were advised of adequate sunlight exposure (30
min/d). Eighteen patients received oral vitamin D3 (cholecalciferol 60,000 IU/wk), 7 received calcitriol (1, 25 dihydroxycholecalciferol 0.5–1.0 mcg/d), and 1 was treated with
intramuscular vitamin D3. One patient who had renal tubular
acidosis was also prescribed Shohl’s solution (i.e., an alkalinizing agent), and 2 patients with malabsorption were treated
appropriately for their gastrointestinal diseases.
The BMD at the lumbar spine (i.e., [L1, L2, L3, L4], left
hip [total], and nondominant forearm [distal and middle onethird radius]) was measured by DXA (Hologic-QDR 4500A).
The reference database used was formed by age- and sexmatched Caucasian subjects. Machine calibration was done
daily before use, and it was operated by 2 densitometry operators who had the required skill and experience in this technique. Precision estimates of the technique were usually
given as the percent coefficient of variation or standard deviation (SD). The SD was often used to construct absolute confidence intervals around a measurement and to compute the
smallest change between 2 measurements that cannot be attributed to measurement error. Minimum significant difference (95% confidence interval) 5 2 O2 SD.
Journal of Clinical Densitometry
Paired t-tests were used to compare results after treatment.
Statistical significance was set at p ! 0.05.
Results
The baseline characteristics, and the initial laboratory and
BMD measurements are shown in Tables 1 and 2. The patients included both sexes and were from a wide age range.
They manifested typical clinical, radiographic, and laboratory
features of frank osteomalacia.
Clinical Evaluation
All but one patient had skeletal symptoms attributable to
osteomalacia; this one patient with celiac sprue presented
only with tetany (i.e., positive Chvostek’s sign and Trousseau’s sign) and no skeletal symptoms of osteomalacia. The
most common presenting complaint was bone pains present
in 22 of 26 patients (85%). They were described by the majority of patients as a dull unrelenting aching sensation in
the bones, and they were elicited by applying minimal pressure with thumb on the sternum, anterior tibia, radius, and
ulna.
Proximal muscle weakness was present in 69% of the patients with varying severity. Of 26 patients, 4 (15%) with very
severe muscle weakness were bedridden or wheelchairbound. Four of 26 patients (15%) sustained pathological fractures of the pelvis and hip.
Diet history revealed inadequate intake of dairy products
in all patients (250 mL of milk or equivalent) and poor sunlight exposure (!15 min/d) in about 75% of the patients.
Mean duration of symptoms was 14 mo.
Diagnostic Studies
Hypocalcaemia was present in 8 of 21 patients (38%), hypophophatemia in 8 of 21 (38%), serum total alkaline phosphatase was elevated in 20 of 21 (95%), serum intact PTH
was elevated in 11 of 11 (100%), and serum 25-hydroxy vitamin D (25[OH] D) was low in 17 of 17 (100%). Serum levels
of 25 (OH) vitamin D were !10 ng/mL in all patients.
At baseline, BMD was low at all three sites (see Table 2),
although the T-scores and Z-scores showed a wide range. The
Z-scores were below 22.0 SD in 15 patients (60%) at the
lumbar spine (L1–L4), in 20 patients (77%) at the hip, and
in 3 of 4 patients (75%) at the radius.
There were no significant correlations between baseline
BMD at the various sites (Z-scores) and initial serum total alkaline phosphatase, PTH, and 25[OH] D. There were no significant correlations between serum 25[OH] D and PTH and
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Bhambri et al.
Table 1
Baseline Characteristics (n 5 26)
Age (y), (mean 6 SD)
Sex
Body mass index (kg/m2),
(mean 6 SD)
Etiology
Clinical presentation
Difficulty walking/waddling
gait
Bedridden/wheelchair-bound
Muscle weakness/myopathy
Bone/muscle pain
Pseudo fractures
(Loozer’s zones)
Fractures
Tetany
39 6 15, range:11–63
19 females, 7 males
27 6 7, range: 15–42
Nutritional, 23,
malabsorption, 2, renal
tubular acidosis, 1
n 5 7 (27%)
n 5 4 (15%)
n 5 18 (69%)
n 5 22 (85%)
n 5 12 (46%)
n 5 4 (15%)
n 5 1 (4%)
Abbr: SD, standard deviation.
between serum 25[OH] D and serum total alkaline phosphatase. Plain X-rays of the pelvis and femur showed pseudo
fractures (looser zones) in 12 of 26 patients (46%).
Treatment
The patients were followed-up for a mean (6SD) period of
7.7 mo (66.3 mo, range: 2.3–34.5). During follow-up, the
doses of calcium and vitamin D were adjusted based on clinical and laboratory parameters. Clinical and biochemical resolution of symptoms occurred in 2.8 mo (61.4 mo, mean
[6SD]) after initiation of treatment (range, 1–7.2 mo). This
was clinically evident by complete disappearance of bone
and muscle pains, and radiologically evident by healing of
pseudo fractures. The only exceptions were those who had severe proximal myopathy and bone deformities in whom the
symptoms did improve significantly, although they did not
completely disappear. Serum PTH levels fell within the reference range before the serum alkaline phosphatase levels did.
However, the serum total alkaline phosphatase in 3 patients
and the PTH in 1 patient remained elevated up to 9 months
after clinical improvement. No patient sustained additional
fracture during follow-up.
Changes in BMD
Lumbar Spine
The mean percent changes (6standard error of the mean
[SEM]) in BMD at the lumbar spine (Fig. 1) was: 25%
(64) in patients who had follow-up DXA scans between
1.5 and 3 mo from baseline (n 5 7), 26% (65) between 3
and 6 mo (n 5 15), 51% (68) between 6 and 9 mo (n 5 8),
39% (69) between 9 and 12 mo (n 5 6), 44% (614) between
12 and 15 mo (n 5 3), 32% (612) between 15 and 24 mo (n
5 2), and 39% (67) between 24 and 36 mo (n 5 2).
The mean change in absolute BMD (gm/cm2) (6 SEM) at
the spine (Fig. 2) was: 10.19 (60.03) from baseline between
1.5 and 3 mo (n 5 14), 10.208 (60.049) between 3 and 6 mo
(n 5 9), 10.297 (60.157) between 6 and 9 mo, (n 5 3),
10.24 (60.053) between 9 and 12 mo (n 5 10), and 10.26
(60.126) between 12 and 15 mo, (n 5 2).
The mean change in absolute BMC (gm) (6SEM) at the
spine (Fig. 3) was: 111.42 (61.96) from baseline between
1.5 and 3 mo (n 5 12), 115.74 (62.98) between 3 and 6
mo (n 5 8), 117.81 (65.57) between 6 and 9 mo (n 5 6),
112.96 (62.82) between 9 and 12 mo (n 5 9), 124.68
(69.45) between 12 and 15 mo (n 5 2), and 113.88
(65.91) at more than 15 mo (n 5 3).
Total Hip
The mean percent changes (6SEM) in BMD of the femoral neck (Fig. 1) was 14% (63) in patients who had follow-up
DXA scans between 1.5 and 3 mo from baseline (n 5 7), 16%
(62) between 3 and 6 mo (n 5 15), 57% (613) between 6
and 9 mo (n 5 8), 35% (68) between 9 and 12 mo (n 5 6),
68% (617) between 12 and 15 mo (n 5 3), 63% (624) between 15 and 24 mo (n 5 2), and 63% (632) between 24
and 36 mo (n 5 2).
Table 2
Baseline Laboratory and BMD Measurements
Initial laboratory tests (mean 6 SD)
Calcium (mg/dL) (n 5 21)
Phosphorus (mg/dL) (n 5 21)
Alkaline phosphatase (U/L) (n 5 21)
Intact PTH (pg/mL) (n 5 11)
25-hydroxy vitamin D (ng/mL) (n 5 17)
Baseline BMD measurements
Baseline T-scores (mean 6 SD)
Lumbar spine (n 5 26)
Hip (n 5 26)
Forearm (n 5 5)
8.2 6 1.0, range: 5.8–9.4
2.6 6 0.9, range: 0.7–4.4
622 6 595, range: 113–2132
496 6 332, range: 112–1002
3.8 (63), range: 1.5–8.4
(normal 8.4–10.2)
(normal 2.7–4.5)
(normal 39–Z 117)
(normal 10–65)
(normal O20)
22.73 6 1.36, range: 10.36 to 25.18
23.60 6 1.16, range: 21.47 to 26.33
23.04 6 2.68, range: 20.13 to 26.59
Abbr: BMD, bone mineral density; PTH, parathyroid hormone; SD, standard deviation.
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Mean % change in BMD (from baseline)
80
70
60
50
40
30
20
10
0
-10
1.5-3 mo
3-6 mo
6-9 mo
9-12 mo
12-15 mo
15-24 mo
24-36 mo
Time in months
Spine (n=7, 1.5-3 mo; n=15, 3-6 mo; n=8, 6-9 mo; n=6, 9-12 mo; n=3, 12-15 mo; n=2, 15-24 mo & 24-36 mo)
Hip (n=7, 1.5-3 mo; n=15, 3-6 mo; n=8, 6-9 mo; n=6, 9-12 mo; n=3, 12-15 mo; n=2, 15-24 mo & 24-36 mo)
Forearm (n=1, 1.5-3 mo; n=5, 3-6 mo; n=3, 6-9 mo; n=2, 9-12 mo; n=1, 12-15 mo & 15-24 mo & 24-36 mo)
Fig. 1. Mean percent change in bone mineral density (BMD) from baseline vs time interval between baseline and repeat dualenergy X-ray absorptiometry (DXA) measurements.
Forearm
In contrast to these large increases in BMD at the femoral
neck and lumbar spine, the radial BMD showed either no
change or a decrement (Fig. 1). The mean percent changes
(6SEM) in BMD at the radius were 10.25% in patients
who had follow-up DXA scans between 1.5 and 3 mo from
baseline (n 5 1), -3.46% (62) between 3 and 6 mo (n 5 5),
-1.23% (60.8) between 6 and 9 mo (n 5 3), 11.32%
(60.2) between 9 and 12 mo (n 5 2), 21.71% between 12
and 15 mo, 22.64% between 15 and 24 months, and
21.4% between 24 and 36 months (n 5 1 for each time
interval).
The mean change in absolute BMD (gm/cm2) at the forearm (Fig. 2) was –0.007 from baseline between 3 and 6 mo
(n 5 1), -0.005 between 6 and 9 mo (n 5 1), 10.005 between
9 and 12 mo (n 5 2), and -0.009 between 12 and 15 mo (n 5 1).
The mean change in absolute BMC (gm) at the forearm
(Fig. 3) was –0.09 (60.03) from baseline between 1.5 and
3 mo (n 5 3), 10.07 (60.16) between 3 and 6 mo (n 5 3),
10.26 (60.37) between 6 and 9 mo (n 5 3), 10.66
(60.61) between 9 and 12 mo (n 5 2), 10.46 (60.82)
between 12 and 15 mo (n 5 2), and -0.64 at more than 15
mo (n 5 1).
The Z-scores at the hip and lumbar spine improved dramatically from a baseline of a low BMD, whereas the radial
0.4
Mean change in absolute BMD (gm/cm2)
The mean change in absolute BMD (gm/cm2) (6 SEM) at
the hip (Fig. 2) was 10.08 (60.017) from baseline between
1.5 and 3 mo, 10.15 (60.05) between 3 and 6 mo, 10.21
(60.105) between 6 and 9 mo, 10.21 (60.052) between 9
and 12 mo, and 10.29 (60.158) between 12 and 15 mo.
The mean change in absolute BMC (gm) (6 SEM) at the
hip (Fig. 3) was 14.61 (60.867) from baseline between 1.5
and 3 mo (n 5 12), 13.92 (61.73) between 3 and 6 mo
(n 5 8), 17.63 (63.13) between 6 and 9 mo (n 5 6),
16.45 (61.64) between 9 and 12 mo (n 5 9), 112.8
(65.62) between 12 and 15 mo (n 5 2), and 18.34 (65.21)
at more than 15 mo (n 5 3).
0.35
0.3
0.25
0.2
0.15
0.1
0.05
0
-0.05
1.5-3 Mths
3-6 Mths
6-9 Mths
9-12 Mths 12-15 Mths
Time
Spine n=14, 1.5-3 mths; n=9, 3-6 mths; n=3, 6-9 mths; n=10, 9-12 mths; n=2, 12-15 mths;
Hip n=14, 1.5-3 mths; n=9, 3-6 mths; n=3, 6-9 mths; n=10, 9=12 mths; n=2, 12-15 mths
Forearm n=1, 3-6 mths; n=1, 6-9 mths; n=2, 9-12 mths; n=1, 12-15 mths
Fig. 2. Mean change in absolute bone mineral density
(BMD) from baseline vs time interval between baseline and repeat dual-energy X-ray absorptiometry (DXA) measurements.
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Bhambri et al.
30
Change in BMC (gms)
25
20
15
10
5
0
1.5-3 Mths
3-6 Mths
6-9 Mths
9-12 Mths
12-15 Mths
>15 Mths
Time interval (months)
-5
Spine1.5-3 mths, n=12; 3-6 mths, n=8; 6-9 mths, n=6; 9-12 mths, n=9; 12-15 mths, n=2; >15 mths, n=3"
Hip1.5-3 mths, n=12; 3-6 mths, n=8; 6-9 mths, n=6; 9-12 mths, n=9; 12-15 mths, n=2; >15 mths, n=3"
Forearm 1.5-3 mths, n=3; 3-6 mths, n=3; 6-9 mths, n=3; 9-12 mths, n=2; 12-15 mths, n=2; >15 mths, n=1"
Fig. 3. Mean change in absolute BMC from baseline versus time interval between baseline and repeat dual-energy X-ray
absorptiometry (DXA) measurements.
Z-scores remained low and relatively unchanged (Table 3).
The improvements in the Z-scores at the hip and lumbar spine
continued well beyond clinical and biochemical recovery.
However, the deficit in the hip ( p 5 0.016) and forearm
( p 5 0.038) Z-score after treatment was found to be significant as compared with that in the spine ( p 5 0.498). There
were large initial increases in the BMD at the lumbar spine
and hip in the first few months of treatment, reflecting the
rapid mineralization of the unmineralized osteoid, followed
by a slower but positive rate of change (Figs. 4 and 5). The
radial BMD did not show any significant change (Fig. 6).
Nine patients underwent more than 2 serial BMD measurements at the lumbar spine and hip (Figs. 4 and 5). These individual plots show rapid and large initial increases in the
BMD followed by a slower rate of improvement. Increases
in the BMD from baseline persisted beyond 30 months of follow-up in 2 patients. Four of the previously mentioned 9 patients had more than 2 BMD measurements at the radius
(Fig. 6). The radial BMD did not change significantly, despite
a corresponding increase at the spine and hip (compare Figs.
4, 5, and 6). This persisted even after 30 months of treatment
in one patient.
Discussion
Table 3
Changes in Average Z-Score From Baseline
Time (mo)
No. of patients
1.5 to 3 mo
7
7
15
15
4
8
8
2
6
6
1
7
7
3
3 to 6 mo
6 to 9 mo
9 to 12 mo
12 to 36 mo
Follow-up Z-Score
Spine
Hip
Spine
Hip
Forearm
Spine
Hip
Forearm
Spine
Hip
Forearm
Spine
Hip
Forearm
21.38
22.22
20.46
21.80
22.97
10.16
21.22
21.50
20.37
20.52
25.88
10.74
20.70
22.81
Osteomalacia belongs to a group of disorders characterized
by defective or delayed bone mineralization (3). Secondary
hyperparathyroidism from hypovitaminosis D leads to an increased bone turnover, which causes cortical thinning and increased cortical porosity due to increased net endosteal
resorption (4) These changes in cortical bone are irreversible.
An increase in the local rate of turnover also leads to substantial increase in the volume of osteoid (unmineralized matrix)
with a corresponding fall in BMC and BMD; these changes
are greater in the cancellous than the cortical bone. Low
BMD is not required for establishing the diagnosis of osteomalacia, but the large increases, as observed in the serial
BMD measurements during the course of treatment, help in
providing retrospective confirmation of the diagnosis and
also help in assessing the response to treatment. Osteomalacia
and rickets are widely prevalent and endemic in some developing countries such as India due to suboptimal nutrition
(1,2). Also, a high prevalence of hypovitaminosis D has
been observed in otherwise healthy Indians (5,6). Inadequate
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50
90
40
80
70
60
50
40
30
20
0
20
10
0
-10
-20
-30
-50
0
2
4
6
8 10 12 14 16 18 20 22 24 26 28 30 32 34
Time (in months)
Fig. 4. Percent change in bone mineral density (BMD) of
the lumbar spine (n 5 9) of 9 different patients.
sunlight exposure, skin pigmentation, inadequate dietary intake, lack of fortification of food with vitamin D and altered
vitamin D metabolism in Indians are thought to be responsible for the high incidence of vitamin D deficiency in India.
Histomorphometric studies show that mineralization resumes rapidly, usually within a week, upon commencing
treatment of osteomalacia and rickets (7,8). Mineralization
of accumulated osteoid is manifested by large increases in
vertebral and hip bone mineral density. However, similar
gains are not seen at cortical sites such as the forearm, as
the cortical thinning and porosity due to secondary hyperparathyroidism are perhaps irreversible (4,9). In a series of 17 patients with osteomalacia due to intestinal malabsorption, there
100
90
80
70
60
50
40
30
20
10
0
30
-40
10
% BMD change (from baseline)
125
0
2
4
6
8 10 12 14 16 18 20 22 24 26 28 30 32 34
Time (in months)
the hip (n 5 9) of 9 different patients.
0
3
6
9
12
15
18
21
24
27
30
33
Time (in months)
the forearm (n 5 4) of 4 different patients.
were increases in BMD at the lumbar spine by 27% and at the
hip by 33%, but there was a 3% decline at the forearm during
treatment (10).
Our study shows large increases in BMD at the lumbar
spine and hip (50–60%), over a few months following treatment of osteomalacia. Changes of such magnitude are only
seen with metabolic bone diseases like osteomalacia, which
are in contrast to that observed in osteoporosis in which the
increase in BMD produced by anticatabolic agents is in the
range of 2–10% over 1–7 yr, and by anabolic agents such
as PTH the range is 10–15% over 2–3 yr (11). Almost all
the patients in our study had nutritional osteomalacia. Improvements in the hip and vertebral BMD and Z-scores in
our study are similar to the previous reports on nutritional osteomalacia (12,13), but they are certainly more than the BMD
changes observed in studies on osteomalacia due to other etiologies. It has been observed that the usual calcium intake in
Indians is inadequate (below 500 mg/d) (2). Although detailed dietary calculations were not performed for our patients, most of them had poor intake of milk and dairy
products and were likely to be deficient in calcium in addition
to vitamin D. Correction of this calcium deficient state with
calcium supplementation, along with treatment of vitamin D
deficiency, may have contributed to the dramatic changes in
the hip and vertebral BMD seen in our patients. The amount
and rate of change in BMD of individual patients was variable, probably due to differences in the severity and duration
of the mineralization defects (Figs. 4 and 5). At the time when
most patients had marked clinical and biochemical improvement (average, 3 mo) the vertebral and hip BMD, although
improved from baseline, had not recovered completely (Table
3). The rate of increase in BMD at these sites was more rapid
in the initial months due to rapid re-mineralization, and subsequently slowed down but continued to increase for up to
34.5 mo of follow-up.
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126
Interestingly, 5 patients continued to demonstrate increases
in vertebral and hip BMD beyond apparently the ‘‘normal’’
range. In these patients, urine and serum fluoride levels were
done to rule out the presence of fluorosis. The values were
within the normal range. The clinical and physiological implications of these changes remains unclear and further follow-up
will show if BMD is maintained at these ‘‘higher’’ levels.
In our study, the radial BMD was low at baseline and did
not improve even after 30 mo of treatment (Fig. 6). This finding is similar to previous studies in which radial BMD was
assessed during treatment, and it probably reflects irreversible
cortical bone loss due to secondary hyperparathyroidism (4).
Adequate calcium and vitamin D nutrition are important
determinants of bone mineral mass, not only during the
growth period but also during adulthood and older age
(14,15). Healthy Indian women have lower BMD in comparison with their Caucasian counterparts (16), and this
may reflect poor nutrition of calcium and vitamin D. Supplementation with calcium and vitamin D has been shown to increase bone density and reduce hip fractures (17), with
greater benefits seen in those with lower dietary intakes
(18). This is particularly relevant in India.
In otherwise healthy persons concerned about fracture prevention, the basic assumption that low BMD is a reliable indicator of bone matrix deficiency is reasonable because the
ratio of mineral to matrix varies between fairly narrow limits.
However, this does not hold true for osteomalacia in which
this relationship between matrix and mineral is markedly disrupted because of impaired mineralization (19). In osteomalacia, low BMD does not reflect bone loss unless the process of
healing of osteomalacia is complete. Therefore, it is required
that all patients with low BMD should be screened for osteomalacia before commencing the treatment of osteoporosis. It
has been proposed that the earlier age of presentation and
equal sex distribution of osteoporosis in India may be in
part due to the high prevalence of subclinical and clinical
vitamin D deficiency and the consequential secondary hyperparathyroidism that leads to an irreversible accelerated agerelated bone loss (20). Thus, there is a need for implementing
measures to prevent vitamin D deficiency, as well as for diagnosing and treating osteomalacia early, and also for an adequate duration to reduce the deleterious effects of secondary
hyperparathyroidism on skeletal health.
In conclusion, our study shows that BMD measurement is
a useful tool in the management of osteomalacia. Although
BMD measurement is not required for the diagnosis of osteomalacia, serial BMD measurements can assess the initial severity of the mineral deficiency and response to therapy, and
can also provide retrospective confirmation of the diagnosis
of osteomalacia. With treatment, clinical and biochemical improvement occurs rapidly within the first few months; however, the bone mineral deficits take longer to correct. Large
and rapid increases in vertebral and hip BMD are observed
in the first few months followed by slow improvement.
Thus, it is important to continue treatment until a satisfactory
improvement in BMD is achieved. However, similar gains in
BMD are not seen at cortical bone sites such as the forearm.
Bhambri et al.
Acknowledgments
We wish to thank Ms. Rupinder for help with the DXA
scan reports and Mr. R. Ravishanker for help with the reference articles.
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3. Parfitt AM. 1996 Osteomalacia and Related Disorders In: Metabolic Bone Disease and Clinically Related Disorders, 3rd ed.
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Changes in Bone Mineral Density Following Treatment of Osteomalacia Original Article Bhambri,

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