Material and methods

The samples were derived from 178 patients (90 girls, 88 boys) diagnosed with short stature seeking therapy at the Department of Endocrinology, Namazi Hospital, Faculty of Medicine, University of Medical Sciences, in Shiraz, Iran. The patients ranged in age from 8 years 2 months to 17 years 9 months. After paraclinical and hand-wrist evaluation, the patients were further divided into familial (76: 38 girls, 38 boys) and nonfamilial (102: 52 girls, 50 boys) groups. To have a sample that better represents the total population of familial short-stature patients, if 2 or more persons were related, only 1 was enrolled in the study. Our selection criteria included patients with height below the fifth percentile, no history of previous trauma or injury to the wrist and neck areas, and no malformations of the cervical vertebrae whether congenital or acquired.

Cephalometric views were obtained on the same day as the hand-wrist radiography. All radiographs were taken with the same equipment (cephalometer PM 2002 EC Proline, KV 85; Planmeca, Helsinki, Finland). Other parameters, including source-to-object and object-to-film distances and x-ray beam characteristics, were identical for all subjects. All assessments were performed by 2 observers, a board-certified oromaxillofacial radiologist (Sh.Sh.) and a resident of orthodontics (A.K.) trained by the radiologist before the study. The observations were made in a semidark room on a radiographic view box for best possible contrast of the views. A black cover was used for viewing the films, with a window showing only the area of cervical vertebrae C2 through C4. This cover omitted the light from the surrounding structures, hence enhancing the viewer’s focus on the desired field of view. Furthermore, using this cover helped to eliminate a possible source of bias from the surrounding structures in the craniofacial complex. The viewers performed a secondary assessment 6 months after the initial observation to determine the intraobserver agreement.

The hand-wrist radiograph was taken from the patient’s left hand according to the conventional method for hand-wrist radiography. Skeletal maturation was determined using the method of Fishman. The lateral cephalometric views were analyzed to determine the cervical vertebral stages according to the method of Hassel and Farman. The observers were blinded for both hand-wrist and lateral cephalometric radiography separately and were unaware of the patients’ chronologic ages.

Fishman’s method consists of 11 stages of development, and Hassel and Farman’s method has 6 stages. To assess the agreement of the 2 methods more easily, Fishman’s method was converted to 6 stages. Each 2 stages were merged into one, and the 11th stage was called stage 6.

We calculated descriptive statistics by determining the means and standard deviations of the chronologic ages for the 6 stages of the CVM. The degree of agreement between hand-wrist and CVM stages with each classifier was assessed by calculation of the contingency coefficient and the weighted kappa statistic. The weighted kappa statistic was used for interobserver and intraobserver agreement. According to Altman’s classification method, agreement ranges from 0 to 1 (poor: κ <0.2; fair: 0.2 < κ <0.4; moderate: 0.4 < κ <0.6; good: 0.6 < κ <0.8; very good: κ >0.8). Statistical analyses were performed with SPSS software (version 11; SPSS, Chicago, Ill).

Results

We studied 76 persons with familial short stature and 102 persons with nonfamilial short stature. Table I shows the subjects’ distributions by sex and chronologic ages, grouped by CVM stage and short-stature state. As shown in Table I , in the familial short-stature group, stages 3, 4, and 5 appeared earlier in the boys, and stages 1, 2, and 6 appeared earlier in the girls. In the nonfamilial short-stature group, nearly every stage (except stage 1) appeared earlier in the girls than in the boys. The reproducibility of all the assessments was good. For interobserver agreement, the weighted kappa statistics for hand-wrist assessments and CVM assessments were 0.81 (95% confidence interval [CI], 0.79-0.83) and 0.89 (95% CI, 0.88-0.91), respectively. The weighted kappa statistics for intraobserver agreement were 0.94 (95% CI, 0.92-0.96) for hand-wrist assessments and 0.96 (95% CI, 0.95-0.97) for CVM assessments. The associations between hand-wrist stage and CVM stage were assessed for subjects according to their sex and short-stature state ( Tables II and III ). As shown in Tables II and III , lower stages of hand-wrist maturation were associated with lower CVM stages. Again, the higher the hand-wrist stage, the higher the CVM stage. Values of contingency coefficients and weighted kappa showed a highly significant association between familial short-stature and nonfamilial short-stature subjects ( Table IV ).

Table III

Associations between CVM stage and hand-wrist (HW) maturation in nonfamilial short-stature subjects

Sex	CVM stage	HW 1	HW 2	HW 3	HW 4	HW 5	HW 6	Total
Female	1	11	2	0	0	0	0	13
	2	3	4	2	0	0	0	9
	3	0	1	3	2	1	0	7
	4	0	0	1	4	1	1	7
	5	0	0	0	2	6	1	9
	6	0	0	0	0	2	5	7
Total		14	7	6	8	10	7	52
Male	1	8	2	0	0	0	0	10
	2	2	5	3	0	0	0	10
	3	0	1	6	3	0	0	10
	4	0	0	0	5	1	0	6
	5	0	0	0	1	5	2	8
	6	0	0	0	0	1	5	6
Total		10	8	9	9	7	7	50

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