Evaluation and comparison of safety, convenience and cost of administering intravenous pamidronate infusions to children in the home and ambulatory care settings.

The use of bisphosphonates in children to treat low bone mineral density has increased. Safety and efficacy of pamidronate has been previously demonstrated. However, little research has been done on pamidronate infusion in the home health setting for patients with metabolic bone disease. Data were collected via a survey to assess satisfaction and convenience of infusions. Adverse events were measured by collecting calcium levels before and after infusions. Infusion costs were estimated from the standard orders from one home health agency and our infusion center. We found no difference in the rates of hypocalcemia between the two groups. The survey results showed high satisfaction for both groups, with higher scores in the home health group for convenience and stress. Home health infusions showed lower cost and less absenteeism from school and work. Home health-based pamidronate infusion appears to be safe, less expensive, and is associated with high patient satisfaction.

A retrospective review of initial bisphosphonate infusion in an inpatient vs. outpatient setting for bisphosphonate naïve patients.

BACKGROUND: The purpose of this study was to evaluate the safety and convenience of initial bisphosphonate infusion therapy in inpatient and outpatient settings for patients with low bone mineral density. METHODS: All data were collected from retrospective chart reviews of heterogeneous groups of patients. Abnormal findings prior to the infusion and side effects during the infusion were documented. Patients were contacted following the infusion to discuss post-infusion adverse events. RESULTS: The majority of both outpatients (80%, n=44) and inpatients (50%, n=27) did not experience any adverse events related to the infusion. Some patients reported minor adverse events that were expected. Only one of the inpatients had a severe adverse event (SAE) after the infusion. CONCLUSIONS: For patients at low risk for severe reactions to treatment, the infusion center appears to be a safe and possibly more convenient treatment setting for both the patient and the hospital, although more expensive for the patient at our institution.

Echocardiographic phenotype in osteogenesis imperfecta varies with disease severity.

BACKGROUND AND OBJECTIVES: Our purpose was to investigate cardiovascular abnormalities in children with osteogenesis imperfecta (OI). METHODS: Two hundred children (100 OI, 100 matched volunteers) were prospectively studied. Aortic and left ventricular (LV) measurements were performed using transthoracic echocardiography. Patients were typed according to modified phenotypical Sillence classification as published in the Nosology and Classification of Genetic Skeletal disorders: 2015 Revision. RESULTS: Patients (age 9.6±4.1 years, body surface area 1.08±0.47 m2) consisted of OI types: 1 (n=44), 3/4 (n=54), 4 (n=1) and 15 (n=1). The 95% CIs for Z-score of aortic annulus, sinus, sinotubular junction and ascending aorta for OI were 0.43 to 0.73, 0.56 to 0.94, 0.28 to 0.70 and 0.78 to 1.24, respectively. In type 1, sinus, sinotubular junction and ascending aorta diameters were 2.29 cm, 1.81 cm and 2.05 cm, respectively, which did not differ compared with controls. The LV dimensions were larger in type 1. In type 3/4, aortic dimensions were larger than controls at all levels: annulus (1.61 vs 1.50 cm, p<0.001), sinus (2.19 vs 2.05 cm, p=0.001), sinotubular junction (1.77 vs 1.64 cm, p<0.001) and ascending aorta (1.98 vs 1.82 cm, p<0.001), but LV dimensions were normal. CONCLUSIONS: Cardiovascular effects are identifiable in childhood even in mild forms of OI. Aortic dilation was the predominant finding, while valvular abnormalities were infrequent. Patients with more severe skeletal pathology (types 3/4) have more significant findings. Aortic and LV dilation in type 1 vs type 3/4 appears to differ based on the biochemical mechanism of disease.

Osteogenesis imperfecta caused by PPIB mutation with severe phenotype and congenital hearing loss.

Osteogenesis imperfecta (OI) is an inherited disorder of connective tissue typically caused by defects in either COL1A1 or COL1A2. A number of other genes causative of this disorder have been found, including PPIB, which forms one subunit of the prolyl 3-hydroxylase enzyme complex. Patients with homozygous or compound heterozygous mutations in this gene have OI with a trend toward lethal or severe phenotype. We present a Native American female with prenatal diagnosis of OI. Long bones were shortened with significant rhizomelia. At birth, fractures were present in ribs, humerii, and femurs. She had significant respiratory disease at birth, and required oxygen throughout her life. She also had recurrent pneumonias, one of which ultimately caused her death at age 16 mo. She also had significant bilateral sensorineural hearing loss. Molecular testing showed that the patient was homozygous for a single nucleotide substitution in PPIB (c. 136-2A>G). Patients with OI caused by PPIB mutations have had variable disease, but with majority of either with perinatal lethality or progressively deforming severe disease. Patients with OI due to PPIB mutation have shown some differences in phenotype. There appears to be a trend toward rhizomelic shortening and less severe bowing of the extremities, as compared to patients with comparably severe OI caused by COL1A1 or COL1A2 mutation. Congenital hearing loss may be an inconsistent feature of this condition, or may have co-occurred in our patient for unrelated reasons. Still, patients with OI caused by PPIB mutation should have appropriate early and regular management of their hearing.