Case report: rare skeletal manifestations in a child with primary hyperparathyroidism.

BACKGROUND: Primary hyperparathyroidism (PHPT) is uncommon among children with an incidence of 1:300,000. This diagnosis is often missed in children in contrast to adults where it is detected at a pre symptomatic stage due to routine blood investigations. Etiology of PHPT can be due to adenoma, hyperplasia or rarely carcinoma. CASE PRESENTATION: A 12 year old Sri Lankan girl presented with progressive difficulty in walking since 1 year. On examination she had bilateral genu valgum. Skeletal survey revealed valgus deformity of knee joints, bilateral subluxation of upper femoral epiphysis(SUFE), epiphyseal displacement of bilateral humeri, rugger jersey spine and subperiosteal bone resorptions in lateral aspects of 2nd and 3rd middle phalanges. There were no radiological manifestations of rickets. Metabolic profile revealed hypercalcemia with hypophosphatemia. Intact parathyroid hormone levels were elevated at 790 pg/ml. Vitamin D levels were deficient. She had low bone mineral density with Z score of -3.4. Vitamin D supplementation resulted in worsening of hypercalcemia without reduction in PTH levels. Tc 99 Sestamibi uptake scan showed abnormal tracer retention in left inferior pole of thyroid. A large parathyroid gland was removed with histology favoring parathyroid adenoma. Post operatively she developed hypocalcemia. Bilateral osteotomy was done for SUFE and further surgeries for correction of limb deformities planned. CONCLUSION: PHPT in children is usually diagnosed late when irreversible organ damage has occurred. Children can present with non specific symptoms involving gastrointestinal, musculoskeletal, renal and neurological systems. PHPT can cause disarray in bone and epiphysis in children during pubertal growth spurt. Genu valgum and SUFE are rare skeletal manifestations in PHPT and only 10 cases of genu valgum and 9 cases of SUFE have been reported up to now. So far no cases have been reported on epiphyseal displacement of humeri. Awareness regarding the occurrence of these rare skeletal manifestations especially during puberty is important for early diagnosis to prevent irreversible outcomes.

The aetiology of rickets-like lower limb deformities in Malawian children.

UNLABELLED: Debilitating rickets-like lower limb deformities are common in children throughout the world, particularly in Malawi, Africa where the causes are unknown. We have identified that Blount disease and calcium deficiency rickets are the likely causes of these deformities and propose calcium supplementation as a potential treatment of Malawian rickets. INTRODUCTION: Surgical correction of rickets-like lower limb deformities is the most common paediatric operation performed at Beit Cure Orthopaedic Hospital, Malawi. The aim of this study was to investigate the aetiology of these deformities. METHODS: Children with a tibio-femoral angle of deformity >20° were enrolled (n = 42, 3.0-15.0 years). Anthropometric and early life and well-being data were collected. Early morning serum and urine samples were collected on the morning of the operation for markers of calcium and phosphate homeostasis. Knee radiographs were obtained, and the children were diagnosed with either Blount (BD, n = 22) or evidence of rickets disease (RD, n = 20). As BD is a mechanical rather than metabolic disease, BD were assumed to be biochemically representative of the local population and thus used as a local reference for RD. RESULTS: There were no differences in anthropometry or early life experiences between BD and RD. Parathyroid hormone (PTH), 1,25-dihydroxyvitamin D, total alkaline phosphatase and urinary phosphate were significantly higher and serum phosphate, 25-hydroxyvitamin D (25OHD) and tubular maximal reabsorption of phosphate significantly lower in RD than BD. There was no difference in serum calcium, fibroblast growth factor 23 or markers of iron status between groups. All children had 25OHD > 25 nmol/L. CONCLUSIONS: Vitamin D deficiency is not implicated in the aetiology of RD or BD in Malawian children. The cause of RD in Malawi is likely to be dietary calcium deficiency leading to elevated PTH resulting in increased losses of phosphate from the bone and glomerular filtrate. The causes of BD remain unclear; there was no evidence in support of previously suggested risk factors such as being overweight or starting to walk early. Prior to surgical intervention, supplementation with calcium should be considered for children with RD.

Characterization of Hip Morphology in Children With Mucopolysaccharidosis Types I and II.

BACKGROUND: The purpose of this study is to describe the natural history of hip morphology in patients with mucopolysaccharidoses (MPS) I and MPS II. METHODOLOGY: This is a retrospective radiographic analysis of 88 hips in 44 children with MPS I and II. Radiographs were examined to determine hip migration, femoral head sphericity, and acetabular dysplasia at different ages throughout childhood. In individual hips, change in morphology and rate of change were analyzed. RESULTS: There was a high rate of hip migration and femoral head dysplasia in both MPS I and MPS II. Progressive migration was seen in three quarters of hips and progressive femoral head deformity in over half of hips. Acetabular dysplasia was variable, ranging from normal to severely dysplastic, but did not change with time. Overall, hips were more dysplastic in MPS I than MPS II. CONCLUSIONS: Hip morphology is variable in MPS I and MPS II ranging from almost normal to severely dysplastic. Some hips do not deteriorate with time and thus surgical intervention may not be necessary in all cases. Deterioration is slow allowing time to plan a holistic approach to treatment. LEVEL OF EVIDENCE: Level IV-case series.

[Operational mechanism modification of bone mechanostat in an animal model of nutritional stress: effect of propranolol]. / Modificación del mecanismo operacional del mecanostato óseo en un modelo de estrés nutricional por efecto del propranolol.

INTRODUCTION: Propranolol (P) treatment exerts a preventive effect against the detrimental consequences to bone status in mildly chronically food-restricted growing rats (NGR) by an increment in cortical bone and by improving its spatial distribution. OBJECTIVE: To study the effect of beta-blocker on operational mechanism of bone mechanostat in an animal model of nutritional stress. MATERIAL AND METHODS: Weanling male Wistar rats were randomly assigned to four groups: control (C), C + P (CP), NGR and NGR + P (NGRP). C and CP rats were fed freely with the standard diet. NGR and NGRP rats received, for 4 weeks, 80% of the amount of food consumed by C and CP respectively, the previous day, corrected by body weight. Propranolol (7 mg/kg/day) was injected ip 5 days per week, for four weeks in CP and NGRP rats. C and NGR received saline injections at an identical dosage regimen. Body weight and length were determined during the experimental period. Dietary intake was registered daily. Animals were sacrificed after 4 weeks of food restriction. Immediately, cuadriceps, femur and tibiae from each animal were dissected and weighed, and histomorphometric and mechanical studies were performed. Serum a-CTX, osteocalcin, intact PTH, calcium and phosphorous were determined. Body protein (% prot) was measured in all groups. RESULTS: Food restriction induced detrimental effects on body and femoral growth, load-bearing capacity (Wf), % prot and cuadriceps weight in NGR us. C (p < 0.01). beta-blocker did not modify anthropometric and bone morphometric parameters in NGRP and CP us. NGR and C, respectively (p > 0.05). However, Wf NGRP vs. NGR was significantly higher (p < 0.01). alpha-CTX was significantly higher in NGR vs. C (p < 0.01). No significant differences were observed in alpha-CTX levels between CP, NGRP and C (p > 0.05). Serum osteocalcin, intact PTH, calcium and phospho- rous showed no significant difference between groups (p > 0.05). CONCLUSION: These results suggest that modeling increase in bone mass and strength in NGRP rats could be due to an anticatabolic interaction of the beta-blocker propranolol on operational mechanism of bone mechanostat in an animal model of nutritional stress.

Congenital chondrodystrophy of unknown origin in beef herds.

Congenital chondrodystrophy of unknown origin (CCUO), often referred to as 'acorn calf disease' or congenital joint laxity and dwarfism (CJLD), has been reported in beef cattle in Canada, the United States, Europe, South Africa, New Zealand and Australia. An association of CCUO with grazing drought-affected pastures, feeding hay-only or silage-only diets or supplementation with apple pulp suggests a nutritional cause such as a mineral deficiency. This review compares published reports on CCUO in order to identify common features among outbreaks and to provide a basis for future research into the condition. A protocol for investigation of outbreaks is provided to improve the outcome of future comparisons.

Displasias óseas: a propósito de una historia familiar / Bone dysplasias: a presentaion of a family history

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The accrual of bone mass during childhood and puberty.

PURPOSE OF REVIEW: To assess factors that influence the tempo of bone mass accrual with emphasis on obesity, exercise, and nutritional factors. RECENT FINDINGS: The prevalence of childhood obesity has increased dramatically throughout the world. Recent studies suggest that adiposity may be detrimental to development of bone strength parameters, and bone mass accrual during growth. Weight-bearing exercise during prepubertal and peripubertal period appears to enhance bone strength parameters. Maternal ultraviolet B radiation exposure and vitamin D status has been shown to have a positive effect on neonatal bone status, which appears to track up to the prepubertal period. Administration of vitamin D with or without calcium, but not calcium alone, during the prepubertal period might be an important 'window' for improving skeletal mineralization. SUMMARY: Obesity in children appears to be detrimental to development of bone strength parameters and bone mass accrual. Weight-bearing exercise during prepubertal and peripubertal period and vitamin D supplementation during pregnancy, infancy, and peripubertal period might be important for bone mass accrual. However, adequately powered randomized controlled trials with follow-up into adulthood are needed to determine if these interventions improve the tempo of bone mass accrual.

Impaired gastric acidification negatively affects calcium homeostasis and bone mass.

Activation of osteoclasts and their acidification-dependent resorption of bone is thought to maintain proper serum calcium levels. Here we show that osteoclast dysfunction alone does not generally affect calcium homeostasis. Indeed, mice deficient in Src, encoding a tyrosine kinase critical for osteoclast activity, show signs of osteopetrosis, but without hypocalcemia or defects in bone mineralization. Mice deficient in Cckbr, encoding a gastrin receptor that affects acid secretion by parietal cells, have the expected defects in gastric acidification but also secondary hyperparathyroidism and osteoporosis and modest hypocalcemia. These results suggest that alterations in calcium homeostasis can be driven by defects in gastric acidification, especially given that calcium gluconate supplementation fully rescues the phenotype of the Cckbr-mutant mice. Finally, mice deficient in Tcirg1, encoding a subunit of the vacuolar proton pump specifically expressed in both osteoclasts and parietal cells, show hypocalcemia and osteopetrorickets. Although neither Src- nor Cckbr-deficient mice have this latter phenotype, the combined deficiency of both genes results in osteopetrorickets. Thus, we find that osteopetrosis and osteopetrorickets are distinct phenotypes, depending on the site or sites of defective acidification.

Adolescent tibia vara, nonossifying fibroma, and bipartite patella in a nationally ranked adolescent karate competitor.

I describe a case of adolescent tibia vara, a contralateral nonossifying fibroma of the tibia, and bipartite patella, which occurred in an adolescent karate competitor of normal stature. The association of this unusual triad supports the hypothesis that each process has a shared traumatic etiology.

Osteopetrosis. Current clinical considerations.

Osteopetrosis is an inherited skeletal condition characterized by increased bone radiodensity. There are three clinical groups: infantile-malignant autosomal recessive, fatal within the first few years of life (in the absence of effective therapy); intermediate autosomal recessive, appears during the first decade of life but does not follow a malignant course; and autosomal dominant, with full-life expectancy but many orthopaedic problems. The infantile variant shows a myelophthisic anemia, granulocytopenia, and thrombocytopenia, and patients eventually die from infection or bleeding or both. Neurologic sequelae include cranial nerve compression (optic nerve, blindness; auditory nerve, deafness; facial nerve, paresis), hydrocephalus, convulsions, and mental retardation. Radiographs show uniform bone density without corticomedulary demarcation, broadened metaphyses, "bone within a bone" or endobone phenomena (tarsals, carpals, phalanges, vertebra, ilium), and thickened growth plates if there is superimposed rickets. Transverse pathologic fractures occur, often followed by massive periosteal bone formation. Computed tomographic scans, magnetic resonance imaging, and bone scans provide specific information. Iliac crest bone biopsy is valuable to quantitate osteoclast and marrow changes by light and electron microscopy. Medical treatments involve high-dose calcitriol to stimulate osteoclast differentiation and bone marrow transplantation to provide monocytic osteoclast precursors. Orthopaedic problems in the intermediate and autosomal dominant forms include increased fractures, coxa vara, long-bone bowing, hip and knee degenerative arthritis, and mandibular and long-bone osteomyelitis. Cranial nerve compression also occurs. Osteotomy, plating, intramedullary rodding, and joint arthroplasty can be done, but are difficult because of bone hardness.

Response of bone and enamel formation to nutritional supplementation and morbidity among malnourished Guatemalan children.

The effects of changes in nutritional and health status upon bone and enamel development are examined in a sample of 63 rural Guatemalan children (24 females, 39 males). The number of ossified hand-wrist centers at 3 years and the number of linear enamel hypoplasias (LEH) in approximately 0-3 year zones of developing teeth were used to monitor the response of bone mineralization and enamel matrix formation to illness and nutritional supplementation. Numbers of ossified centers and LEH were compared across sex, supplementation, and morbidity groups. Enamel matrix secretion responded positively to increased supplementation. Children who received less than 34.25 kcal/day in supplement had more LEH than those who received more supplement. No differences in ossification status were found between supplementation groups. These data suggest that enamel formation may be more sensitive to changes in nutritional status than is bone mineralization. Disruptions of bone and enamel formation were both associated with frequent illness. Children who were ill more than 3.6% of the time had more LEH and fewer ossified hand-wrist centers than children who were less frequently ill. Conclusions regarding relative environmental sensitivity must take into account the specific aspects of dental and skeletal development examined.

[Value of a phosphorus supplemented formula for premature infants]. / Intérêt d'une augmentation de l'apport phosphoré dans un lait pour le prématuré.

The fortuitous discovery of bone mineralization abnormalities in premature babies fed a medium chain triglyceride supplemented formula and exhibiting satisfactory weight gains prompted us to perform calcium and phosphorus balance studies. The infants studied had no major neonatal disorders and were not vitamin D-deficient. Urine assays detected no phosphorus and demonstrated an increase in calcium excretion, suggesting an inadequate phosphorus intake. This hypothesis was confirmed by the appearance of urinary phosphates with a decrease in calcium losses following supplementation of the formula with phosphorus.

Zinc deficiency in pheasant chicks fed practical diets.

A disease syndrome characterized by abnormal feathering and varus deviation of the tarsometatarsus spontaneously occurred in pheasant chicks fed a practical commercially prepared diet. The addition of supplemental Zn to the commercial diet was effective in alleviating the clinical signs, even though the commercial mix had Zn levels that met the published pheasant chick requirement. Supplemental arginine was ineffective in reducing the severity of the clinical signs. Also, when the diet was mixed in a laboratory setting, pheasant chicks did not develop abnormal feathering and leg bones. Clinical signs caused by feeding the commercial mix were not reproduced by altering dietary calcium and phosphorus levels in the laboratory mix. Neither adding a pellet binder nor removing supplemental Zn from the lab mix produced as severe leg and feather deformities as the commercial mix. Thus, unidentified dietary factors are capable of causing a Zn-deficiency syndrome in pheasant chicks fed practical diets with analyzed Zn levels meeting the required levels.

[Effect of iron-deficient diets on the formation of bone tissue]. / Vliianie ratsionov s defitsitom zheleza na formirovanie kostnoi tkani.

The effect of the iron-deficient diets on osseous tissue formation was studied in long-term experiments. During intense growth, iron deficiency led to a decrease in the content of hexosamines, in the activity of phosphomonoesterase I and calcium, delay in collagen maturation in the femoral bones, as well as to phosphorus-calcium metabolic disorders. Histological examination revealed thickening of the articular cartilage, an increase in the number and volume of osteocytes, islets of the proliferative osteocytes on the part of the endosteum, and a number of dystrophic abnormalities.

Late sequelae of infantile meningococcemia in growing bones of children.

Multiple, irregular ball-and-socket deformities at the ends of long bones were noted in four children several years after they had had meningococcemia. Even though these lesions were clinically unsuspected at the time of the fulminant disease, they were probably the result of ischemia secondary to septic emboli to the epiphyseal vessels, which occurred at the same time as soft-tissue necrosis elsewhere. The individual lesions were radiologically identical to the metaphyseal cupping that has been reported following trauma to the growth plate.

Ascorbic acid deficiency and hypertrophic osteodystrophy in the dog: a rebuttal.

Plasma ascorbic acid (PAA) in normal Labrador Retriever dogs less than one year of age averaged 1.22 +/- 0.05 mg/dl (x +/- sem) and was significantly higher than the value of 0.89 +/- 0.03, for Labrador Retrievers two years of age and older. No significant diurnal variation in PAA was observed. Oral or intravenous administration of 0.5 or 1.0 g of ascorbic acid (AA) elevated PAA for less than 8 hours. Injection of ACTH caused a significant decline in PAA for the initial 2 days, with variable results thereafter. Labrador Retriever puppies fed a ration high in protein, energy and calcium developed the typical skeletal diseases of overnutrition, including hypertrophic osteodystrophy (HOD). The addition or oral AA (0.5 g twice daily) had no ameliorating effect on the skeletal lesions. Instead AA supplementation resulted in relatively higher serum calcium values which, presumably by enhanced hypercalcitoninism, decreased bone resorption. Thus, AA treatment of dogs with HOD is contraindicated, as it can only aggravate the osseous lesions of HOD. The decreased PAA reported in dogs with HOD is interpreted to be the result of stress from pain.

Twisted legs in broilers.

The effect of various factors on the incidence of leg abnormalities, with particular reference to twisted leg, in broilers was studied. The incidence of twisted legs was influenced by strain and for males was twice that for females. There was also a higher incidence in cages than on litter with the type of cage floor having an effect: broilers reared on floors of metal wire and perforated sheets had more leg problems than those reared on plastic mats and plastic-covered wire. Although vitamin and mineral supplementation had no effect on caged broilers, a restriction of metabolisable energy (ME) intake during the first 14 d after hatching halved the frequency of leg abnormalities compared with those fed ad libitum. Studies of cage size and location of water suggested that a lack of exercise increases the incidence of leg abnormalities.

Investigations of leg abnormalities in chicks consuming high tannin sorghum grain diets.

Studies were conducted into the etiology of leg abnormalities noted in chicks fed high tannin sorghum grain diets. These anomalies were characterized by a bowing of the legs with a swelling of the hock joints. The incidence of these leg problems was found to be markedly higher when the amino acids in the diet provided by soybean meal were replaced by crystalline amino acids. Supplemental vitamins and minerals had no alleviating effect on the leg problem. Bone mineralization was apparently not influenced by tannins as demonstrated by similar bone ash values for chicks fed high or low tannin sorghums. A possible alteration caused by tannin in the organic matrix of bone is discussed. High tannin sorghum depressed chick growth and feed conversion when compared with low tannin sorghum in both sorghum-soybean meal and sorghum-amino acid rations. This growth depression was overcome by supplementing the high tannin sorghum-soybean meal diet with .15% DL-methionine, but no growth response was observed from a similar supplementation of a high tannin sorghum-amino acid diet.