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Recently, a new anthropometric method of accurate lower leg length measurement (knemometry) was introduced. The present study was performed to investigate rigorously its strengths and weaknesses for auxological purposes, and to promote a standardized method of use. The data are based on 6 x 2200 single estimations of the lower leg length in 90 children of both sexes with normal, tall or short stature aged between 2.4 and 17.1 years. The overall technical error of this measurement was found to be 0.16 mm, which is reduced to 0.13 mm if the first estimation within each series of six is ignored. The following sources of systematic error could be detected: intra-daily variation, dependency on physical pressure put on or removed from the leg, vigorous physical activity prior to the measuring procedure, and a slow but significant correlation between day-to-day variation of lower leg length and body weight (r = 0.299, b = 0.372 mm/kg). There was no covariation with atmospheric parameters such as outside temperature, barometric pressure and others. After elimination of a linear trend from the individual growth curves, there was a remaining day-to-day variation of SD = 0.697 mm. This represents real changes of lower leg length and cannot be explained by the technical error of measurement which contributes to less than 10% of the total variation. Some of this day-to-day variation may be explained by non-linearity of growth. Knemometry appears to be a robust and precise new tool for the investigation of short term kinetics of longitudinal growth. Proposals for a standardized use of this technique are given.

Recently a novel and non-invasive technique of lower leg length measurement (knemometry) was introduced. The method estimates the distance between heel and knee in the sitting child with an accuracy of 0.09 mm(SD). Two female patients with anorexia nervosa, aged 14:4 and 13:7 years, weighing minus 27 and minus 38% of normal weight for age, were measured repeatedly with this method within periods of 72 and 129 days during hospitalization und up to 133 days thereafter. During the first 40 days of hospitalization, patient 1 was measured 30 times and showed significant shrinkage of the lower leg length of -0.040 mm/day (P less than 0.001). Over the remainder of her hospital stay her mean lower leg length increment still was much less (+0.036 mm/day) than that expected just by increase of soft tissue due to rapid weight gain (+0.126 kg/day). The second patient also showed significant shrinkage of lower leg length during a 4 month period after discharge from the hospital (-0.009 mm/day, P less than 0.01). This is the first demonstration of long term lower leg shrinkage in children. Its origin remains unclear, but this shrinkage is clearly distinct from either arbitrary changes of lower leg length due to errors of measurement or changes of body diameters due to temporary alterations of soft tissue (i.e. during periods of weight loss). We speculate that progressive atrophic changes of the epiphyseal plates still open in both patients may account for the observed long term shrinkage of lower leg length.

Daily growth of the lower leg in a child receiving alternate day oral steroids for Crohn's disease was measured by knemometry. Growth occurred on days free of treatment. This may represent a direct observation of the growth sparing effect of alternate day steroid medication.

Evidence has accumulated that predictions of annual or half-annual growth rates are of limited validity when derived from extrapolations of short term growth rates. In order to investigate whether the poor predictive qualities of short sections of individual growth curves are caused by non-linearity of human growth, we have studied 73 healthy children, aged 2.9 to 15.9 years, with standard deviation scores for body height ranging between -3.3 and +3.0. The children were measured between 18 and 106 times once or twice per week throughout periods of 180 to 306 days by knemometry, a novel and noninvasive technique of accurate lower leg length measurement. Non-linearity of growth was found in about 70% of those children who could be measured more than 35 times. 45 children provided evidence for a characteristic up-and-down pattern of lower leg growth velocity consisting of sharp growth spurts ('mini growth spurts') alternating with periods of decreased growth velocity every 30 to 55 days. This pattern seemed to appear spontaneously, though in some cases we found a marked coincidence between periods of growth arrest and intermittent infectious illness.

The early effects of human growth hormone (hGH) were investigated by knemometry, a recently described technique of measuring lower leg length. In 14 growth hormone deficient children, the mean increase in the lower leg length was 0.47 +/- 0.10 (SE) mm within 24 h of a single intramuscular injection of 4 IU hGH. This increase occurred after about 80% of the single injections and was highly significant (p less than 0.01). 48 h after an injection, a slight but not significant reduction of the lower leg length was observed (-0.15 +/- 0.09 [SE]). These effects led to a marked zig-zag pattern of growth when hGH was given thrice weekly.

The growth promoting potential of GRF(1–29)NH2 was studied in nine boys with short stature over three periods of 3 months. Their short stature was due to partial hGH deficiency/hGH neurosecretory dysfunction and was diagnosed by arginine and insulin stimulation tests and hGH nocturnal profiles. Four patients (Group I) were given GRF, 3–4 μg/kg s.c. b.d. during the first period of 3 months, and after an interval of 1 month, the same dose once daily during the second treatment period of 3 months. Five patients (Group II) were given GRF, 3–4 μg/kg s.c., once daily during the first and b.d. during the second 3 months of therapy. After a second interval of 1 month without any GRF treatment, the third 3-month period for both groups consisted of one daily injection of GRF, 8–10 μg/kg s.c. at 19.00 hours. Total body height and lower leg length were measured by stadiometry and knemometry, respectively. GRF intravenous bolus tests were performed in each patient following fasting, before and at the end of the first and second 3-month periods. Serum IGF–1 and urinary hydroxyproline excretion were determined monthly. Stadiometric growth rate, determined over the whole study period of 11 months including the treatment-free intervals, increased from 4.92 cm/year to 5.97 cm/year (p>0.05). Mean knemometric growth rates increased from 0.28 mm/week before therapy, to 0.35 mm/week during the one injection/day period at low dose, to 0.39 mm/week (p

A novel and non-invasive technique of growth measurement is introduced. By this method the length of the human lower leg is measured with an accuracy of 0.1 mm. Thus, growth velocities can be estimated within a few weeks. In the present study the immediate changes of growth velocity are demonstrated, following the transfer of growth hormone administration from three times weekly im to daily sc in 9 growth hormone deficient children, age 7.4 to 20.5 years. The first observation period (3 times weekly im administration) ranged from 32 to 72 days, the second observation period (daily sc administration) ranged from 160 to 267 days). During the study, the total weekly dosage of growth hormone remained unchanged (12 IU/m2/week). In all 9 patients growth velocity increased significantly after the transfer of application. Mean growth velocity of the lower leg rose from 0.04 mm/day up to 0.065 mm/day. Mean growth velocity of total body height rose form 4.8 cm/year up to 6.9 cm/year. In addition, differential lower leg growth rates of 3 to 4 week periods were established in all 9 patients, revealing a significant catch-up growth spurt immediately following the transfer of application. During this spurt mean lower leg growth velocity rose form 0.04 mm/day up to 0.091 mm/day. This marked increase of lower leg growth rates lasted for only a few weeks and was followed by a period of decreased growth velocity. On the long run, growth velocity shifted upward in a wave-like pattern, stabilizing on a significantly higher level than before the transfer of application.

Two patients, aged 5 and 12 years, with Silver-Russell type dwarfism are presented. As shown by standard tests and examination of the spontaneous nocturnal hGH secretion, there was only mild regulative hGH deficiency. HGH treatment was started with daily subcutaneous injections at age 5.5 years (height 90.3 cm, −6.1 SDS, bone age 2.75 years) and 12.6 years (height 125.7 cm, −3.7 SDS, bone age 8.75 years), respectively. Treatment was monitored by serial somatomedin-C (SM-C) determinations and by knemometry (lower leg measurement). SM-C values increased in both patients by 10.5 and 4.8 fold, respectively, and remained above the prepubertal range (>2.5 U/ml) during the treatment periods of 1.5 years. Pretreatment knemometric growth rate was high (after a somatomedin generation test) in patient 1 (0.7 mm/week) and low in patient 2 (0.31 mm/week). It remained at the same level in patient 1 (0.67 mm/week) and increased markedly in patient 2 (0.46 mm/week). During a treatment interruption, in both patients, knemometric growth rates fell to 0.33 and 0.30 mm/week, respectively. After resumption of treatment, now with biosynthetic hGH, growth rates increased again in patients 1 and 2 to 0.64 and 0.48 mm/week, respectively. This lower leg growth pattern was parallelled by similar changes in total body growth velocity. Even after the relatively short treatment period of 14 to 16 months, a slight net gain in statural height could be observed, as standard deviation scores for bone age increased.

Wit, J. M., Teunissen, D. M., Waelkens, J. J. J. and Gerver, W. J. (Departments of Paediatrics of the University Hospital for Children and Youth, Utrecht, Catharina Hospital, Eindhoven and University Hospital, Maastricht, The Netherlands). Comparison of short-term lower leg growth with statural growth in children treated with growth promoting substances. Acta Paediatr Scand [Suppl] 337:40, 1987. Lower leg growth was determined by knemometry in 11 children with short stature, before and during therapy with growth promoting drugs. The growth response of lower leg length was determined by comparing growth velocities over periods of 6 weeks. The growth response of total body height was determined by comparing the growth velocity during 3 months of therapy with the growth velocity over 1 year before therapy. Significant knemometric growth responses were always associated with positive height responses, hut smaller knemometric responses were associated with positive as well as negative height responses.

We studied the differential inhibitory effects of conjugated oestrogens on lower leg length and standing height increments in 17 excessively tall girls compared to a control group of 17 tall healthy untreated girls. Standing height, lower leg length and body weight were recorded at weekly or monthly intervals. Standing height velocity dropped from 150 microns/day to 122 microns/day, whereas daily weight gain increased from 17 to 48 g/day during oestrogen treatment. The oestrogen induced decrease of standing height velocity could be explained by a marked inhibition of lower leg growth velocity from 42 microns/day to 30 microns/day (native data) or 35 microns/day to 8 microns/day (data corrected for weight gain) (P less than 0.001), whereas no differences of trunk growth velocity could be detected. Thus, the findings strongly suggest that pharmacological doses of oestrogens only affect epiphyseal growth.

Wales, J. K. H. and Milner, R. D. G. (Department of Paediatrics, University of Sheffield, Sheffield, UK). Knemometry as a predictor of response to somatrem in Turner's syndrome. Acta Paediatr Scand [Suppl] 337:37, 1987. The response of 13 children with Turner's syndrome to somatrem, 2 IU/day, has been determined for a 4-week period of treatment using knemometric measurements, and compared to 6 months of treatment assessed by conventional auxology. In this small series, knemometry was able to predict those children in whom hGH therapy was not beneficial.

Thirty-seven children with intrauterine growth retardation (IUGR) were enrolled in a 3-mo longitudinal study. Weight, length, and knee-heel length (by knemometry) were measured at birth and at 7, 14, 30, 60, and 90 d. GH, IGF-I, IGF binding protein (BP)-3, IGFBP-1, and C-peptide were measured at birth and at 2 mo. IGFBP-3 Western immunoblotting and proteolytic activity assay were also performed. Twenty-five newborns with birth weight appropriate for gestational age were chosen as controls. At birth IUGR newborns showed levels of GH and IGFBP-1 significantly higher, and IGF-I, IGFBP-3, and C-peptide significantly lower than control subjects. At 2 mo GH and IGFBP-1 levels decreased, whereas IGF-I, IGFBP-3, and C-peptide rose, attaining the concentrations found in control subjects at birth. Baseline peptide levels as well as their 2-mo variations did not correlate with the gain in weight, supine length, and knee-heel length recorded at 3 mo. Fourteen of nineteen IUGR cord blood samples showed the presence of the intact approximately 42-39-kD IGFBP-3 doublet and the major approximately 29-kD fragment. At 2 mo the IGFBP-3 band pattern was characterized by the predominance of a approximately 18-kD fragment in 6 of 19 tested IUGR infants. The incubation of 2-mo IUGR samples with normal adult serum induced the appearance of the approximately 18-kD band, which was not modified by the addition of EDTA. These results suggest that: 1) the IGF-related growth-promoting mechanism is impaired in IUGR children at birth but is fully restored at 2 mo; 2) the cord blood levels of GH, IGF-I, IGFBP-3, IGFBP-1, and C-peptide are not predictive of the weight and length gain during the first 3 mo of life; 3) IUGR children have at least two different IGFBP-3 proteases, one cation-dependent protease that is present at birth and able to yield the major approximately 29-kD IGFBP-3 fragment and a second one, with a different activation timing, which exhibits cation independence and induces the formation of a approximately 18-kD IGFBP-3 form.

Aim: To compare and evaluate a mini-knemometer with a simple and inexpensive electronic caliper with regard to precision, handling error (technical error) and estimation of growth velocity. Methods: Thirty-five prematurely born infants, with a median gestational age of 29 (range 24–33) wk and a median birthweight of 960 (range 480–2480) g, were measured on 409 different occasions with both instruments. On each occasion, five independent readings were made. Results: There was no significant difference in precision between the two instruments, when measuring growth velocity over a 4 wk period (median 0.41, range 0.10–0.59 mm d−1). The handling error in this study, calculated as the mean standard deviation, was 0.36 (SD 0.18, coefficient of variation 0.38%) mm for the simple electronic caliper and 0.59 mm for the mini-knemometer. Short-term growth was detectable within 2 d when growth velocity was normal. Conclusion: Longitudinal measurement of lower leg length is a gentle and useful complementary method for assessing growth in preterm infants. An inexpensive electronic caliper is well suited for routine use in clinical practice, with measurements taken once or twice a week.

To assess the growth promoting potential of GRF, we studied so far 4 boys (age 5 - 13 yrs) with short stature (height SDS -2.2 to -3.8) due to partial HGH deficiency, diagnosed by arginin and insulin stimulation tests and nocturnal HGH secretion profile. None of them received any prior hormonal therapy. Before, after 2 weeks and at the end of 12 weeks of GRF therapy, each child had an i.v. GRF 1-29 bolus test (2 μg/kg, AM, fasted) with determination of plasma HGH, basal serum somatomedin C (SMC) and urinary hydroxyproline excretion (OHP). Lower leg length, measured by knemometry was determined under standard conditions once a week for 3 - 15 months before and twice a week during GRF treatment. Synthetic GRF 1-29 was given s.c. in a dose of 3 - 4 μg/kg b.i.d., at 0700 and 1900 h. After 2 weeks of GRF treatment, the peak HGH response after GRF i.v. stimulation increased from (means) 31 to 74 ng/ml. SMC increased from 1.07 to 2.25 IU/ml and OHP from 119 to 210 μg/mg creatinine. Knemometric growth rate increased by 1.6 to 2.8-fold from (means) 0.44 to 0.93 mm/week. Such increased growth rates were never observed in any of these patients during the pretreatment period. The knemometric growth patterns during CRF therapy appear to be similar to those observed during the initiation of HGH substitution therapy. Our preliminary data suggest that GRF 1-29, given s.c. twice daily, induces longitudinal growth via increased endogenous HGH and SMC secretion and thus may be of therapeutic value in GRF deficient short children.

SHORT TERM RESPONSE TO SOMATREM IN TURNER SYNDROME ASSESSED BY KNEMOMETRY AND CONVENTIONAL AUXOLOGY

It is now possible to study short-term growth by knemometry, a non-invasive technique measuring the exact distance between heel and knee in sitting children. During the measurement the lower leg length (LLL) is determined by repeatedly moving the child's knee under the measuring board. Each single measurement consists of six independent estimations, the SD of which is