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Horacio Plotkin

Publications and source records attributed to Horacio Plotkin.

14 recordsLinked to original sources
PubMed2006

Low doses of pamidronate to treat osteopenia in children with severe cerebral palsy: a pilot study.

The aim of this study was to test the efficacy of low doses of pamidronate in increasing bone mineral density (BMD) in non-ambulatory children and adolescents with cerebral palsy (CP). Twenty-three non-ambulatory children and adolescents (12 females, 11 males; mean age 10y [SD 5y], range 4y 1 mo-17 y 11 mo) with severe spastic quadriplegic CP and low BMD were recruited from a multidisciplinary clinic. Severity of CP was graded at Level IV (n=10) and Level V (n=13) using the Gross Motor Function Classification System. Patients received intravenous pamidronate (4.12 mg/kg/y, maximum 45 mg/d) every 4 months. Lumbar spine and femoral neck BMD were measured at baseline and after 4 and 12 months. Twelve months after the first dose of pamidronate there was a significant increase in lumbar spine and femoral neck BMD (p<0.01 for both sites) and z scores compared with baseline values (p<0.01 for both sites). Mean BMD z scores increased 1.6 points for femoral neck and 1.9 points for lumbar spine after 12 months of pamidronate treatment. Serum intact parathyroid hormone increased significantly and cross-linked N-teleopeptide of type I collagen decreased significantly at 12 months. No significant side effect was noted. Low doses of pamidronate are well tolerated and significantly increase BMD in non-ambulatory children and adolescents with CP.

Adolescent↗
PubMed2004

Syndromes with congenital brittle bones.

BACKGROUND: There is no clear definition of osteogenesis imperfecta (OI). The most widely used classification of OI divides the disease in four types, although it has been suggested that there may be at least 12 forms of OI. These forms have been named with numbers, eponyms or descriptive names. Some of these syndromes can actually be considered congenital forms of brittle bones resembling OI (SROI). DISCUSSION: A review of different syndromes with congenital brittle bones published in the literature is presented. Syndromes are classified in "OI" (those secondary to mutations in the type I pro-collagen genes), and "syndromes resembling OI" (those secondary to mutations other that the type I pro-collagen genes, identified or not). A definition for OI is proposed as a syndrome of congenital brittle bones secondary to mutations in the genes codifying for pro-collagen genes (COL1A1 and COL1A2). SUMMARY: A debate about the definition of OI and a possible clinical and prognostic classification are warranted.

Collagen↗
PubMed2003

Osteogenesis imperfecta types I, III, and IV: effect of pamidronate therapy on bone and mineral metabolism.

Cyclical iv therapy with pamidronate improves the clinical course in children and adolescents with osteogenesis imperfecta (OI). In this study we evaluated the effect of this therapy on bone and mineral metabolism in 165 patients with OI types I, III, and IV (age, 2 wk to 17.9 yr; 86 girls and 79 boys). All patients received iv pamidronate infusions on 3 successive days, administered at age-dependent intervals of 2-4 months. During the 3 d of the first infusion cycle, serum concentrations of ionized calcium dropped by 0.14 +/- 0.008 mmol (mean +/- SE; P < 0.001), and serum PTH levels transiently almost doubled (P < 0.001). At the same time, urinary excretion of the bone resorption marker type I collagen N-telopeptide related to creatinine (uNTX/uCr) decreased by 61-73% (P < 0.001). Two to 4 months later, ionized calcium had returned to pretreatment levels, and uNTX/uCr remained 30-35% lower than at baseline (P < 0.001). During 4 yr of pamidronate therapy (n = 40 patients), ionized calcium levels remained stable, but PTH levels increased by about 30% (P < 0.01). uNTX/uCr, expressed as a percentage of the age- and sex-specific mean value in healthy children, decreased from 132 +/- 13% (mean +/- SE) at baseline to 49 +/- 3% after 4 yr of therapy (P < 0.001). In conclusion, serum calcium levels can decrease considerably during and after pamidronate infusions, requiring close monitoring especially at the first infusion cycle. In long-term therapy, bone turnover is suppressed to levels lower than those in healthy children. The consequences of chronically low bone turnover in children with OI are unknown at present.

Adolescent↗
PubMed2003

Effect of pamidronate treatment in children with polyostotic fibrous dysplasia of bone.

Intravenous infusions with the bisphosphonate compound pamidronate decrease bone pain and reportedly can lead to refilling of dysplastic lesions in adults with fibrous dysplasia (FD) of bone. Here we describe the effects of this treatment approach in 18 children and adolescents (age at start of therapy, 6.2-17.5 yr; eight girls) with polyostotic FD, who received pamidronate for 1.2-9.1 yr (median, 3.8 yr). Treatment cycles with pamidronate (1-1.5 mg/kg.d on 3 consecutive days) were given every 4 months. Levels of serum alkaline phosphatase and urinary collagen type I N-telopeptide were elevated at baseline and decreased continuously during the first 3 yr of therapy. There was no radiographic evidence of filling of lytic lesions or thickening of the bone cortex surrounding the lesions in any patient. Histomorphometric results in dysplastic bone tissue of patients receiving pamidronate (n = 7; time of therapy, 1.4-4.8 yr) were similar to those of patients without medical therapy (n = 9). No serious side effects were noted. In conclusion, pamidronate therapy appears to be safe in children and adolescents with polyostotic FD. However, we found no clear evidence that pamidronate has an effect on dysplastic lesions in such patients.

Adolescent↗
PubMed2003

Bone mass, size, and density in children and adolescents with osteogenesis imperfecta: effect of intravenous pamidronate therapy.

Cyclical intravenous therapy with pamidronate improves the clinical course in children and adolescents with osteogenesis imperfecta (OI). In this study, we evaluated the effect of this therapy on lumbar spine bone mass (bone mineral content [BMC]), size (bone volume [BV]), and density (volumetric bone mineral density [vBMD]). Results from 56 patients (age, 0.2-15.9 years; 25 girls) on long-term pamidronate treatment were compared with those of 167 patients who had not received pamidronate before densitometry. In all patients who received pamidronate, BMC, BV, and vBMD increased above levels expected for untreated patients (p < 0.001 in each case). After 4 years of treatment, BMC, BV, and vBMD were 154%, 44%, and 65% higher, respectively, in treated than in untreated patients who were matched for age and OI type. A multiple regression model showed that baseline BMC was negatively associated with the increase in BMC. In conclusion, the bone mass increase in pediatric OI patients receiving pamidronate is caused by increases in both bone size and density. Patients with larger deficits in bone mass at baseline have a more marked bone mass gain during therapy.

Adolescent↗
PubMed2003

Height and weight development during four years of therapy with cyclical intravenous pamidronate in children and adolescents with osteogenesis imperfecta types I, III, and IV.

OBJECTIVES: Treatment with pamidronate improves the clinical course in children with osteogenesis imperfecta (OI), but theoretically might affect longitudinal growth. In this study we analyzed growth during cyclical intravenous pamidronate treatment in children and adolescents (age.04-15.6 years at baseline) with moderate to severe forms of OI types I, III, and IV. METHODS: The effect of 1 year of pamidronate treatment on height and weight was analyzed in 116 patients (OI-I, N = 29; OI-III, N = 42; OI-IV, N = 45). The results of 4 years of therapy were evaluated in 41 children (OI-I, N = 12; OI-III, N = 14; OI-IV, N = 15). RESULTS: Baseline height was low for age in all OI types. After 1 year of pamidronate therapy, height z scores had increased significantly in OI-III (by 0.3 +/- 0.8, mean +/- standard deviation; P =.04) and did not change in OI-I and OI-IV. Weight z scores increased significantly in OI-I (by 0.2 +/- 0.4, P =.01). After 4 years of pamidronate therapy, mean height z scores increased significantly in OI-IV (by 0.41 +/- 0.71, P =.04), whereas nonsignificant trends to increase were found for OI-I and OI-III. When height was expressed as a percentage of the result expected for untreated patients with the same OI type, long-term pamidronate therapy was associated with a significant height gain in all 3 OI types (P <.001). Eight patients who reached final height after 3.0 +/- 1.0 years of treatment were taller on average than expected for untreated patients (P =.04). CONCLUSIONS: Four years of cyclical intravenous pamidronate treatment led to a significant height gain in moderately to severely affected OI patients.

Adolescent↗
PubMed2003

Rapid increase in grip force after start of pamidronate therapy in children and adolescents with severe osteogenesis imperfecta.

OBJECTIVE: To examine changes in grip force during pamidronate therapy in children and adolescents with severe osteogenesis imperfecta (OI). METHODS: Maximal isometric grip force of the nondominant hand was prospectively determined in 42 patients (age at the start of the study: 7.3-15.9 years; 18 girls) with severe forms of OI. Patients were treated with intravenous pamidronate infusions given in 4 monthly cycles, each cycle consisting of 3 infusions (1 mg pamidronate/kg body wt) on 3 successive days. RESULTS: At the start of pamidronate therapy, grip force was low compared with age-specific reference data (age z score mean +/- standard deviation: -2.7 +/- 2.1) but was normal for weight (weight z score: -0.1 +/- 1.8). Four months after the first pamidronate infusion cycle, grip force had increased significantly, whether related to age (age z score: -2.0 +/- 1.8) or to weight (weight z score: 0.6 +/- 1.5). At 2 years after the start of therapy, grip force z scores were not significantly different from the 4-month results. CONCLUSIONS: Maximal isometric grip force markedly increases after a single cycle of intravenous pamidronate in children with severe forms of OI, and this gain in grip force is maintained for at least 2 years.

Adolescent↗
PubMed2002

The effects of intravenous pamidronate on the bone tissue of children and adolescents with osteogenesis imperfecta.

Cyclical pamidronate infusions increase bone mass in children suffering from osteogenesis imperfecta. The histological basis for these effects remains unknown. Therefore, we compared parameters of iliac bone histomorphometry from 45 patients before and after 2.4 +/- 0.6 years of pamidronate treatment (age at the time of the first biopsy, 1.4-17.5 years; 23 girls). Although biopsy size did not change significantly (P = 0.30), cortical width increased by 88%. Cancellous bone volume increased by 46%. This was due to a higher trabecular number, whereas trabecular thickness remained stable. Bone surface-based indicators of cancellous bone remodeling decreased by 26-75%. There was no evidence for a mineralization defect in any of the patients. These results suggest that, in the growing skeleton, pamidronate has a twofold effect. In remodeling, bone resorption and formation are coupled and consequently both processes are inhibited. However, osteoclasts and osteoblasts are active on different surfaces (and are thus uncoupled) during modeling of cortical bone. Therefore resorption is selectively targeted, and continuing bone formation can increase cortical width.

Adolescent↗
PubMed2002

Bone mineralization in polyostotic fibrous dysplasia: histomorphometric analysis.

Fibrous dysplasia (FD) of bone can be complicated by renal phosphate wasting. The effect of hypophosphatemia on normal and dysplastic bone of FD patients has not been well characterized. In this study, we compared serum phosphorus (sPi) levels to histomorphometric findings in 27 iliac bone samples from 23 children and adolescents (aged 4.2-16.4 years) with polyostotic FD. The samples were separated into two groups, based on the presence (n = 10) or absence (n = 17) of a dysplastic lesion within the specimen. Histomorphometric results were compared with those from 18 age-matched control subjects without metabolic bone disease. In dysplastic lesions, trabeculae were clearly thinner and increased in number. Osteoid indices, osteoblast surface per bone surface, and mineralization lag time were elevated in dysplastic areas, but there was no detectable effect of sPi concentrations on these indices. In nondysplastic bone tissue, low sPi levels were associated with mildly increased osteoid thickness and prolonged mineralization lag time. None of the 13 patients in whom hand X-rays were available at the time of biopsy had radiological signs of rickets. In conclusion, low sPi can cause a mild systemic mineralization defect in FD, but the more severe mineralization defect seen in dysplastic lesions is independent of sPi levels. It is debatable whether the mild systemic mineralization defect warrants treatment with oral phosphorus supplementation if signs of rickets are absent.

Adolescent↗
PubMed2002

Comparable bioavailability of two esophago-gastric protective formulations containing pamidronate. A cross-over trial in healthy young adults.

The net absorbable amount of pamidronate (APD), according to AUC values assessed in blood, in the customary dose interval of 24 hours, was found to be similar in 8 healthy young volunteers, who received single doses of 3 capsules of 100 mg APD (AUC0-24 = 510.3 +/- 91.5 micrograms/L x h-1) and 2 tablets of 150 mg (AUC0-24 = 580.5 +/- 117.6 micrograms/L x h-1; p = 0.58) in the fasting state. Both formulations present acid-resistant coatings, designed to protect the mucosa of the upper digestive system from contact with insoluble particles of the bisphosphonates. Tmax values were different, and Cmax values presented a wide inter-individual variation, so that both formulations were not strictly bioequivalent. However, these latter factors were of minor clinical importance given the kinetic features of the bisphosphonates. In conclusion, both formulations afforded comparable bioavailability; that is to say that they can provide a sufficient amount of APD within the studied dose interval, so as to cause similar clinical effects.

Administration, Oral↗
PubMedDate not supplied

Bone healing in children with osteogenesis imperfecta treated with bisphosphonates.

The long-term effects of bisphosphonate treatment in children with osteogenesis imperfecta (OI) are unknown. The aim of this study was to evaluate whether treatment with bisphosphonates interferes with the healing of fractures in a group of children with OI. Seven subjects (6 boys), aged 11.4 +/- 5.95 years, were followed for 2.5 +/- 0.84 years after the start of treatment with intravenous pamidronate (9 mg/kg/y) and/or oral alendronate (5 or 10 mg/d). Orthopaedic surgery of 24 bones was performed after 2.33 +/- 4.14 months of treatment, with 1.6 +/- 0.84 osteotomies per bone. Ambulation was started after 26.1 +/- 32.28 days. Reoperation was required in 8% of the bones due to fracture below primary fixation. Pseudoarthrosis was seen in one fracture, an osteotomy of the proximal femur (14% of the patients, as expected in an OI population). These results suggest that treatment with bisphosphonates at the administered doses does not interfere with fracture healing. Larger and longer studies are warranted.

Adolescent↗