Efficacy and Safety of Percutaneous Epiphysiodesis Operation around the Knee to Reduce Adult Height in Extremely Tall Adolescent Girls and Boys

In Sweden, a common definition of extreme tall stature is an adult height exceeding 200 cm for boys and 185 cm for girls corresponding to approximately 3 SD above the mean. Tall stature is most often caused by genetic factors (constitutional tall stature). However, an underlying disorder must always be considered in tall individuals as many of them need special medical attention. These include homocysteinuria, growth hormone excess, and various syndromes such as Klinefelter, Sotos, Marfan, and Beckwith-Wiedemann syndrome [1, 2].

Extreme tall stature is a common reason for referral to pediatric endocrinology centers in northern European countries. Patients and their families often express a strong desire for intervention aiming to reduce adult height. The treatment options for children with extreme tall stature are limited. To reduce final height (FH), boys have been treated with high-dose testosterone and girls with high-dose estradiol [3, 4]. The treatment was introduced already in 1956, but its use has decreased dramatically in the last two decades, possibly due to a change in attitude towards tall stature and concerns of long-term complications [5]. In a meta-analysis study, hormonal treatment was only found to reduce final height if initiated before a bone age of around 14 yrs in both genders [6]. It was suggested that administration of sex steroids after this age causes extra growth instead of growth inhibition.

Undesired side effects are commonly reported in patients undergoing hormonal treatment for tall stature. For boys, one of the most common complaints reported is acne. Other documented side effects are weight gain, muscle ache, gynecomastia, hypertrichosis, behavioural changes, and aggressiveness [7, 8]. For girls, side effects include nausea, headache, elevated serum triglycerides, calf cramps, and weight gain [8–10]. More serious concerns with the treatment include a possible increased risk of venous thrombosis. Studies have shown changes in coagulation parameters [11] although no studies have been able to show an increased risk of venous thrombosis [12]. There is also a fear of a further increased risk of breast cancer [4, 9, 13] and decreased fertility [4]. One study from Australia shows that women who have been on high-dose oestrogen treatment to reduce their final height are more likely to have tried for over a year to get pregnant (relative risk 1.80, 95% CI 1.40–2.30) and to have taken fertility drugs (relative risk 2.05, 95% CI 1.34–3.04). They are also less likely to conceive in any given menstrual cycle although the possibility of conceiving at all is only slightly decreased, possibly due to the availability of fertility treatments. Because of the various side effects associated with hormonal treatment and sometimes limited efficacy, an alternative treatment modality is desired.

Surgical epiphysiodesis performed around the knee has for many years been used to treat leg length discrepancies [14]. In extremely tall boys, the use of bilateral percutaneous epiphysiodesis was recently reported to reduce adult height by approximately 5 cm when performed at a mean bone age of 13.9 years [15]. However, it is important to point out that still this is a controversial treatment as it is being performed in healthy adolescents and further supportive data are lacking.

The aim of our study was to determine the efficacy and safety of bilateral epiphysiodesis around the knee when performed to limit further growth in extremely tall adolescent girls and boys. We included radiological assessments of bone growth and bone angles and a reference group of untreated extremely tall subjects to document the efficacy and safety of bilateral percutaneous epiphysiodesis.

We here report that bilateral percutaneous epiphysiodesis performed around the knee effectively inhibits further leg growth when performed in extremely tall adolescent girls and boys. The operation was more effective when performed at an early bone age. We found the procedure to be safe and no significant side effects were reported.

We here document the efficacy and safety of epiphysiodesis in both girls and boys. Previously the only report of long-term outcome of this procedure has been in boys. The height reduction in our male patient group is in agreement with what was previously reported [15]. We have not only based our data on auxological measurements but also verified the efficacy and safety radiologically. To further strengthen the accuracy of the final height predictions, a validation cohort was recruited.

In both girls and boys, bilateral percutaneous epiphysiodesis reduced the predicted remaining growth from time of surgery by approximately one third. When reviewing studies of hormonal treatment, epiphysiodesis seems to be more efficient in reducing final height. In girls treated at a bone age of 12.5 yrs, the height reduction is around 2 cm with hormonal treatment and around 4 cm with epiphysiodesis [6]. In boys treated at a bone age of 14 yrs, epiphysiodesis results in a final height reduction by around 6 cm whereas hormonal treatment at this bone age results in no height reduction at all according to a meta-analysis [6]. Our results showed that epiphysiodesis was efficient in reducing final height in all patients except for one boy where we believe his predicted remaining growth was underestimated. This assumption is based on the fact that the growth of his upper body (9.0 cm) far exceeded his leg growth (0.9 cm) suggesting that the intervention was indeed effective also in this patient.

With regards to safety, we monitored for short-term side effects such as postoperative infections, pain, or discomfort as well as long-term side effects including any hip-knee-ankle angulations, leg length discrepancies, or abnormal body proportions. The only side effects reported were mild to moderate postoperative pain and one superficial cutaneous infection. Our findings are in agreement with a previous study of epiphysiodesis where no serious side effects were reported either [15]. Although no serious complications occurred, it should be noted that this is an invasive procedure in otherwise healthy individuals. Failure of epiphysiodesis secondary to insufficient ablation of the physis has indeed been reported by others [18]. Therefore, careful diagnostic preoperative evaluation is essential, and the treatment should be performed in a center of expertise ensuring the long-term followup. Regarding body proportions, relative sitting height at final height was indeed closer to the normal than before surgery when being compared to normative tables for the general population [19]. The reason for this is that tall stature is usually characterized by relatively long legs [20]. In most girls, the sitting height percentage remained below the mean at final height. In contrast, most boys had a sitting height percentage which was above the normative population, and in two of them this was more pronounced, most likely linked to the fact that their sitting heights were above the mean already at the time of surgery. At final height, none of the treated patients expressed dissatisfaction with their body proportions. However, an increase in relative sitting height is to be excpected and should be considered before treatment decision is made. We do not believe that the surgical treatment will lead to any long-term side effects in contrast to hormonal treatment for which fear has been raised of side effects such as reduced fertility [4] and breast cancer [11, 13]. Other side effects that have been associated with hormonal treatment, such as hypertension and thrombosis [11], were not seen in our operated patients. Therefore, we regard surgery as the treatment of choice in extremely tall patients with high blood pressure and/or a family history of venous thrombosis.

Final height predictions are known to be imprecise estimates of remaining growth. The most widely used method for prediction of final height was devised by Bayley and Pinneau (BP method). This method is routinely used in clinical practise [6]. At time of surgery, most of our patients were in midpuberty with a mean age of  yrs in girls and  yrs in boys. A previous study has shown that the mean height prediction errors (BP method) at these ages are  cm in girls (13 yrs) and  cm in boys (14 yrs) [6].

In order to reduce any prediction errors, all X-ray images were read by two blinded observers. In an attempt to quantify the potential errors of these predictions, we recruited an untreated reference population of extremely tall females and males. This validation clearly demonstrated that the predication errors were so small that we could ignore it when calculating the efficacy of the treatment. It is important to point out that the untreated reference group did not differ significantly from the treated group, although not being randomly selected. It would of course have been optimal to include a randomized untreated control group, but this was not possible for technical reasons. Nevertheless, the efficacy of the operation was confirmed by radiological leg measurements which is a very reliable method to assess bone growth.

Our data suggest that bilateral percutaneous epiphysiodesis is an efficient and safe method to reduce adult height in extremely tall adolescents. The intervention should not be performed too late, preferably at a bone age not exceeding twelve and a half years in girls and fourteen years in boys. We recommend that a treatment decision is taken before girls have reached a height of 170 cm and boys 185 cm. Hereby, the expected growth reduction will exceed 5 cm as long as the predicted final height is at least 185 cm in girls and 200 cm in boys. The patients should preferably have preoperative evaluation, treatment, and followup in a specialized center with expertise in pediatric endocrinology and pediatric orthopaedic surgery. Further studies are desired to document the efficacy and safety of this relatively new procedure in larger patient groups.