Are Adult Patients with Laron Syndrome Osteopenic? A Comparison between Dual-Energy X-Ray Absorptiometry and Volumetric Bone Densities

Giampiero Igli Baroncelli, Silvano Bertelloni, Laura Galli, Federica Sodini and Giuseppe Saggese

Endocrine Unit, Division of Pediatrics, Department of Reproductive Medicine and Pediatrics, University of Pisa, I-56125 Pisa, Italy

Address correspondence to: Giampiero I. Baroncelli, M.D., Endocrine Unit, Division of Pediatrics, Department of Reproductive Medicine and Pediatrics, University of Pisa, Via Roma 67, I-56125 Pisa, Italy. E-mail: g.baroncelli{at}med.unipi.it.

To the editor:

We have read with great interest the article by Benbassat et al. (1). The study showed that untreated adult patients with Laron syndrome (LS), in addition to dwarfism, have low lumbar and femoral areal bone mineral density (aBMD), due to reduced bone size, but normal volumetric BMD (vBMD) by using volumetric estimates derived from dual-energy x-ray absorptiometry (DXA). Bachrach et al. (2) found similar data in 11 Ecuadorian patients with LS. These results raise an important question: does the GH-IGF-I axis have an effect on BMD.

In children with isolated GH deficiency, we showed that lumbar spine vBMD, derived by a mathematical model of DXA measurements, remained significantly reduced, although to a lesser extent than aBMD (–0.8 ± 0.4 Z score and –2.8 ± 0.5 Z score, respectively). The bone area (BA)/bone volume (BV) ratio was significantly higher in patients than in controls (0.53 ± 0.02 and 0.42 ± 0.08, respectively; {Delta} 21%), due to the fact that in patients, BV was affected to a greater extent than BA (–32% and –15%, respectively) (3). On the basis of the mean densitometric data reported by Benbassat et al. (1), using the method of Katzman et al. (4), we derived additional bone parameters, such as BV and BA/BV ratio, from their patients and controls [lumbar spine, BV 112.7 cm3 and 277.2 cm3 ({Delta} 59%); BA/BV ratio, 0.21 and 0.15 ({Delta} 29%), respectively; femoral neck, BV 14.1 cm3 and 25.5 cm3 ({Delta} 45%); BA/BV ratio, 0.27 and 0.20 ({Delta} 26%), respectively]. These data indicate that lumbar and femoral mean BV values were approximately 50% lower and mean BA/BV ratio was 28% higher in untreated adult patients with LS than in controls, suggesting that the markedly reduced BV may be a main factor affecting the calculation of vBMD in patients with LS. An influence of BV on vBMD measurement by DXA is observed in healthy children and adolescents; girls have higher vBMD values than boys due to the fact that the former have smaller BVs than the latter. By contrast, bone mass and aBMD are higher in boys than in girls because the former have greater bone size than the latter (5). However, although DXA-derived BV is a better parameter than BA for BMD estimates, the mathematical calculation of BV is only a surrogate index of anatomical size, so that it could artificially overestimate the values of vBMD leading to a misinterpretation of results. In other words, the "true" bone density could be really reduced in patients with LS, but DXA measurement is not able to assess it. At any rate, a recent study in a large number of premenopausal women demonstrated that lumbar spine vBMD by DXA was a sensitive marker for the diagnosis of osteoporosis and that it was not correlated with BA (6). Conversely, we cannot exclude the possibility that patients with LS really have a normal BMD; indeed only one patient sustained a fracture (after severe trauma). In agreement with this observation, Bachrach et al. (2) showed a preservation of volumetric bone density and cortical width by histomorphometry, as well as normal bone turnover in patients with LS, suggesting that local production of IGF-I, IGF-binding proteins, or other growth factors could have a role in stimulating bone mineral accretion.

The results of Benbassat et al. (1) do not exclude a role of IGF-I in bone mass accretion because the three patients who had received recombinant IGF-I treatment attained greater adult height, aBMD, or vBMD values. Moreover, Shaw et al. (7) found that lumbar vBMD was slightly reduced in prepubertal children with LS in comparison with controls, but it progressively improved over the 5-yr treatment period with recombinant IGF-I.

Conventional radiographs may provide some qualitative information on osteopenia, such as increased radiolucency, cortical thinning due to endosteal or intracortical resorption; and trabecular rarefaction, as well as morphometric radiogrammetry of metacarpal bones, may be useful to assess a reduced cortical bone mass. Did the authors perform an x-ray study of the skeleton in their patients with LS?

Received November 17, 2003.

References

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