Monthly intravenous alendronate treatment can maintain bone strength in osteogenesis imperfecta patients following cyclical pamidronate treatment.

Objectives Osteogenesis imperfecta (OI) is a skeletal dysplasia characterized by recurrent fractures due to congenital bone fragility. The only bisphosphonate approved for OI in Japan is pamidronate (PAM). To investigate whether monthly intravenous alendronate (ALN) infusions can maintain bone strength in OI children following cyclical PAM treatment. Methods A prospective and non-inferiority study was conducted. Eight school-age OI patients aged 8.5±2.0 years who were treated with cyclical PAM for 6.0±2.3 years were enrolled and switched to monthly intravenous ALN (0.030 mg/kg/month). Changes in L1-4 bone mineral density (BMD) Z-scores, fracture rates, and bone turnover markers for 12 months were analyzed. Results Average BMD Z-scores were -3.0±1.9, -2.9±2.0, and -2.2±2.0 in 12 months before enrollment, at enrollment, and after 12 months of ALN treatment, respectively. BMD Z-scores increased significantly during treatment with both PAM and ALN (p=0.012), and the effect of ALN was not inferior to that of PAM (p=0.67). There was no change in fracture rates (p=0.86) and bone turnover markers during the 12 months before and after enrollment. Additionally, ALN showed no remarkable side effects. Conclusions Our results suggest that monthly intravenous ALN can maintain bone strength after primary usage of cyclical PAM. We concluded that monthly intravenous ALN as a maintenance treatment following cyclical PAM administration can be an option for OI children.

A case of perinatal hypophosphatasia with a novel mutation in the ALPL gene: clinical course and review of the literature.

Hypophosphatasia (HPP) is a metabolic bone disease characterized by failure of bone calcification and vitamin B6 dependent seizures. It is caused by loss-of-function mutations in the ALPL gene. A newborn girl required respiratory support by nasal-directional positive airway pressure at birth, and pyridoxine hydrochloride administration for vitamin B6-dependent seizures observed from day two. Umbilical cord blood showed low alkaline phosphatase (ALP) activity and high pyridoxal phosphate levels. Radiographs showed severe rickets-like appearance of the bones. Genetic analysis of the ALPL gene revealed compound heterozygous mutations, c.1559delT/p.Ser188Pro. We diagnosed her with perinatal severe HPP, and started the patient on asfotase alfa from day six. Following enzyme replacement therapy (ERT), skeletal mineralization and respiratory insufficiency improved with no remarkable side-effects. Crying vital capacity (CVC) was used to evaluate respiratory status, which continuously improved from 13.3 mL/kg (day 22) to 20.6 mL/kg (day 113). Since no seizures occurred, pyridoxine hydrochloride was tapered off at one year of age. Strategies to manage perinatal severe HPP cases following ERT have not been established till date. A review of the literature shows that CVC may be a good indicator for weaning from ventilatory support. In addition, ERT will most likely enable withdrawal of pyridoxine treatment.

Final adult height in long-term growth hormone-treated achondroplasia patients.

The objective of this study was to evaluate the gain in final height of achondroplasia (ACH) patients with long-term growth hormone (GH) treatment. We analyzed medical data of 22 adult patients (8 males and 14 females) treated with GH at a dose of 0.05 mg/kg/day. Optionally, tibial lengthening (TL) was performed with the Ilizalov method in 15 patients and TL as well as femoral lengthening (FL) in 6 patients. Concomitant gonadal suppression therapy with buserelin acetate was applied in 13 patients. The mean treatment periods with GH were 10.7 ± 4.0 and 9.3 ± 2.5 years for males and females, respectively. GH treatment augmented the final height +0.60 ± 0.52 SD (+3.5 cm) and +0.51 ± 1.29 SD (+2.8 cm) in males and females compared to non-treated ACH patients, respectively. Final height of ACH patients that underwent GH and TL increased +1.72 ± 0.72 SD (+10.0 cm) and +1.95 ± 1.34 SD (+9.8 cm) in males and females, respectively. GH, TL, and FL increased their final height +2.97 SD (+17.2 cm) and +3.41 ± 1.63 SD (+17.3 cm) in males and females, respectively. Gonadal suppression therapy had no impact on final height. CONCLUSIONS: Long-term GH treatment contributes to 2.6 and 2.1% of final adult height in male and female ACH patients, respectively.

Measurement of force applied by infant tongue to the nipple during sucking and investigation of the mechanism of tongue movement.

In order to clarify the dynamic mechanisms involved in sucking by infants, we developed an artificial nipple with built-in force sensors and have measured the contact force between the tongue and the artificial nipple in infants including healthy, premature and low birth weight. In this study, we measured the force applied by the tongue on the artificial nipple in 10 healthy infants and in 10 infants who were also tube-fed and investigated the differences in dynamic actions between the two groups to extract factors involved in satisfactory sucking. The results showed that differences in the maximum force applied and in the time to reach the maximum force were found between infants with and without established oral feeding. For an infant to suck satisfactorily, 1) the time for the force to propagate from the tongue tip to the tongue root needs to constitute at least 8 % of the sucking period and 2) the force applied at the tongue tip needs to be at least 50% of the force at the tongue root.

Measurement of tongue-artificial nipple contact force in infants with sucking difficulties.

Infants are known to suckle and ingest breast milk by wrapping the tongue around a nipple, writhing the tongue, and pressing the nipple. However, the dynamic mechanisms of tongue movement are still obscure, and factors related to sucking difficulties of infants are not well understood. We developed an artificial nipple installed with small cantilever-type sensors and directly measured the force applied on the nipple by the tongue. Small force sensors were arranged within the artificial nipple in a two-dimensional matrix of 3 × 2 to measure the force at 6 points. Subjects were 20 healthy infants (Group A) and 5 infants who had difficulty sucking (Group B). The latter could not breastfeed well and were fed from bottles or tubes. Informed consent was provided by the parents or guardians. The measured maximum force at the tip of the nipple was 1.4 ± 0.4 N and 1.2 ± 0.3 N (mean ± SD) in Groups A and B, respectively. At the base of the nipple, the maximum force recorded was 0.8 ± 0.5 N and 0.3 ± 0.3 N (mean ± SD), respectively, showing a statistically significant difference (p<0.05). The sucking period was 0.6 ± 0.1 s (mean ± SD) in both groups. The difference in time necessary to reach the maximum forces between the sensors at the tip and base was 39.7 ± 28.8 ms (mean ± SD) and 37.2 ± 75.9 ms in Groups A and B, respectively.