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Progressive osseous heteroplasia (POH) is a rare autosomal dominant disorder of mesenchymal differentiation characterized by progressive heterotopic ossification (HO) of dermis, deep connective tissues and skeletal muscle. Usually, initial bone formation occurs during infancy as primary osteoma cutis (OC) then progressively extending into deep connective tissues and skeletal muscle over childhood. Most cases of POH are caused by paternally inherited inactivating mutations of GNAS gene. Maternally inherited mutations as well as epigenetic defects of the same gene lead to pseudohypoparathyroidism (PHP) and Albright's hereditary osteodystrophy (AHO). During the last decade, some reports documented the existence of patients with POH showing additional features characteristic of AHO such as short stature and brachydactyly, previously thought to occur only in other GNAS-associated disorders. Thus, POH can now be considered as part of a wide spectrum of ectopic bone formation disorders caused by inactivating GNAS mutations. Here, we report genetic and epigenetic analyses of GNAS locus in 10 patients affected with POH or primary OC, further expanding the spectrum of mutations associated with this rare disease and indicating that, unlike PHP, methylation alterations at the same locus are absent or uncommon in this disorder.

Polyglandular autoimmune syndrome is defined as multiple endocrine gland insufficiencies accompanied by autoimmune diseases of the endocrine and nonendocrine system. After Schmidt introduced a case of nontuberculosis adrenal gland dysfunction with thyroiditis in 1926, Neufeld defined polyglandular autoimmune syndrome by I, II, and III subtypes in 1980 by their presentation of occurrence age, heredity methods, relationship with human leukocyte antigen, and accompanying diseases. We report a case of a 32-year-old female with polyglandular autoimmune syndrome III accompanied by type 1 diabetes mellitus that was treated with insulin (36 units per day) for 11 years. She had insulin deficiency and Hashimoto thyroiditis as an autoimmune disorder. In addition, she had several features similar to Albright's hereditary osteodystrophy including short stature, truncal obesity, round face, short neck, low intelligence (full IQ 84), and decreased memory. Although Albright's hereditary osteodystrophy is morphological evidence of pseudohypoparathyroidism or pseudopseudohypoparathyroidism, she had primary hypoparathyroidism on laboratory results. Here, we report a case of polyglandular autoimmune syndrome III with type 1 diabetes mellitus, autoimmune thyroiditis, and primary hypoparathyroidism, accompanied by clinical features similar to Albright's hereditary osteodystrophy.

Hepatic encephalopathy (HE) is a reversible neuropsychiatric disorder in cirrhotic patients. The cognitive dysfunction and increased accidental falls in HE and osteodystrophy in cirrhotic patients may contribute to orthopedic fractures. This study investigated the fracture incidence and risk factors in cirrhotic patients with HE.In total, 3764 cirrhotic patients with HE were identified from the Taiwan National Health Insurance database between 2000 and 2009. The fracture incidence of the HE patients was compared with that of 3764 age-, sex-, and comorbidity-matched cirrhotic patients without HE and non-cirrhotic controls. Cox proportional hazard models were used to estimate the risk of fracture in the HE patients.Cirrhotic patients with and without HE had comparable increased risks of fracture (p0.05) and cumulative incidences of fracture than controls (log-rank p0.001). The estimated fracture rates were 7.09% for the HE group, 7.72% for the cirrhosis without HE group, and 4.05% for the controls, during the 18-month follow-up. The HE group had a higher incidence rate of skull fractures (IRR=2.61, 95% CI 1.04-6.57), but a lower rate of upper limb fractures (IRR=0.45, 95% CI 0.29-0.70) than the cirrhosis without HE group. Alcoholism, heart failure, and cerebrovascular disease were associated with increased risk of fracture in HE patients.Cirrhotic patients, with or without HE, are at an increased risk of orthopedic fractures. Skull fractures, rather than fractures in weight-bearing bones, are more frequently observed in HE patients, particularly those with comorbidities.

Background: Osteogenesis imperfecta (OI) is a rare congenital genetic osteodystrophy, which has a prevalence of 1:20,000. OI is caused by the mutation of the COL1A1/COL1A2 genes, leading to a deficit of quality and/or quantity in the synthesis of procollagen-α type 1. Seven different forms of diverse clinical entity have been classified by Sillence and Glorieux, although, recently, up to 11 forms characterized by different genetic mutations have been recognized. Patients with OI suffer from extreme bone fragility and osteoporosis, which often predisposes them to frequent fractures. This paper presents the case of a child with OI type IV who, at birth, was also diagnosed with a severe clubfoot (congenital talipes equinovarus) grade III. Patient's mother also suffers from OI type IV. Methods: The treatment was started by placing femoro-podalic corrective casts, according to the Ponseti method, but some unexpected problems occurred during this treatment. When the patient was 3 months of age, we decided to correct the clubfoot before the time limit planned, performing a bilateral posteromedial surgical release. Results: Three weeks after surgery the casts were removed and replaced with bilateral Spica cast-like braces. On the 6th postoperative week, the patient began wearing Bebax corrective shoes, after 1 year ambidextrous orthopedic shoes. Now, he is 2 years old and has started to walk properly without any orthesis. Conclusion: In the presence of an orthopedic pathology associated with OI, it is recommended to manage the patient according to the underlying pathology, always considering the bone fragility associated with OI. The final surgical treatment to correct the clubfoot can be done earlier, if necessary. In our opinion, this uncommon association between OI and clubfoot is non-syndromic. This means that the two congenital diseases are not necessarily included in a singular uncommon genetic syndrome, but the clubfoot was caused by multifactorial causes, especially by both the mother's bisphosphonate drug therapy and the amniocentesis performed during her pregnancy to drain polyhydramnios. In our analysis, those environmental factors could have interacted with an already altered genetic substratum, contributing to develop this rare combination of congenital disorders.

Results are presented of measurements of skeletal blood flow made in 80 patients with painful benign or malignant diseases of the skeleton, excluding patients with Paget's disease. In crush fracture osteoporosis, total bone blood flow was slightly lower than normal although skeletal perfusion was normal. High values of bone blood flow were seen in 14 20 patients with osteomalacia and 3 12 patients with primary hyperparathyroidism. Very high values, comparable to those seen in the most severely affected patients with Paget's disease, were seen in polyostotic fibrous dysplasia, 2 out of 4 cases of Engelmann's disease and 1 out of 3 cases of renal osteodystrophy. Results were less elevated in myositis ossificans, secondary skeletal involvement with breast and prostatic carcinomata, myelomatosis and sympathetic osteodystrophy.

We report a case of chronic osteomyelitis caused by Burkholderia cepacia presenting with multiple bone localizations in an infant affected by end-stage renal disease. In order to avoid the amputation of the extremities, a salvage procedure was attempted: all lesions were curetted completely and filled in with bone cement. At 24 months follow-up all lesions are completely healed.

Dysregulation of skeletal remodeling is a component of renal osteodystrophy. Previously, we showed that activin receptor signaling is differentially affected in various tissues in chronic kidney disease (CKD). We tested whether a ligand trap for the activin receptor type 2A (RAP-011) is an effective treatment of the osteodystrophy of the CKD-mineral bone disorder. With a 70% reduction in the glomerular filtration rate, CKD was induced at 14 weeks of age in the ldlr-/- high fat–fed mouse model of atherosclerotic vascular calcification and diabetes. Twenty mice with CKD, hyperphosphatemia, hyperparathyroidism, and elevated activin A were treated with RAP-011, wherease 19 mice were given vehicle twice weekly from week 22 until the mice were killed at 28 weeks of age. The animals were then evaluated by skeletal histomorphometry, micro-computed tomography, mechanical strength testing, and ex vivo bone cell culture. Results in the CKD groups were compared with those of the 16 sham-operated ldlr-/- high fat–fed mice. Sham-operated mice had low-turnover osteodystrophy and skeletal frailty. CKD stimulated bone remodeling with significant increases in osteoclast and osteoblast numbers and bone resorption. Compared with mice with CKD and sham-operated mice, RAP-011 treatment eliminated the CKD-induced increase in these histomorphometric parameters and increased trabecular bone fraction. RAP-011 significantly increased cortical bone area and thickness. Activin A–enhanced osteoclastogenesis was mediated through p-Smad2 association with c-fos and activation of nuclear factor of activated T cells c1 (NFATc1). Thus, an ActRIIA ligand trap reversed CKD-stimulated bone remodeling, likely through inhibition of activin–A induced osteoclastogenesis.

Context: The term pseudohypoparathyroidism (PHP) was coined to describe the clinical condition resulting from end-organ resistance to parathormone (rPTH), caused by genetic and/or epigenetic alterations within or upstream of GNAS. Although knowledge about PHP is growing, there are few data on the prevalence of underlying molecular defects. Objective: The purpose of our study was to ascertain the relative prevalence of PHP-associated molecular defects. Design: With a specially designed questionnaire, we collected data from all patients (n = 407) clinically and molecularly characterized to date by expert referral centers in France, Italy, and Spain. Results: Isolated rPTH (126/407, 31%) was caused only by epigenetic defects, 70% of patients showing loss of imprinting affecting all four GNAS differentially methylated regions and 30% loss of methylation restricted to the GNAS A/B:TSS-DMR. Multihormone resistance with no Albright’s hereditary osteodystrophy (AHO) signs (61/407, 15%) was essentially due to epigenetic defects, although 10% of patients had point mutations. In patients with rPTH and AHO (40/407, 10%), the rate of point mutations was higher (28%) and methylation defects lower (about 70%). In patients with multihormone resistance and AHO (155/407, 38%), all types of molecular defects appeared with different frequencies. Finally, isolated AHO (18/407, 4%) and progressive osseous heteroplasia (7/407, 2%) were exclusively caused by point mutations. Conclusion: With European data, we have established the prevalence of various genetic and epigenetic lesions in PHP-affected patients. Using these findings, we will develop objective criteria to guide cost-effective strategies for genetic testing and explore the implications for management and prognosis.

Objective: To determine the prevalence of different patterns of renal osteodystrophy in end stage renal failure patients on maintenance haemodialysis visiting at Nephrourology Department, Liaquat University of Medical and Health Sciences, Jamshoro, Pakistan. Methodology: A cross-sectional study was conducted at Nephro-urology Department, Liaquat University of Medical and Health Sciences, Jamshoro, Pakistan from April to October 2015. Fifty-six (56) patients on maintenance hemodialysis were included through non-probability purposive sampling. Various biochemical parameters of renal osteodystrophy were included in the current study. Serum corrected calcium, phosphate, and alkaline phosphatase and iPTH levels. Chi square test was used to determined frequency of renal osteodystrophy in ESRD patients. Results: Mean age was 45.85 ± 13.5 years. 34 (61%) were male and 22 (39%) were female. Renal osteodystrophy was found in 89%. The most common type was secondary hyperparathyroidism (Osteitis Fibrosa Cystica) in 32%. Hyperphosphatemia was observed in 62% while hypercalcaemia in only 7%. Osteomalacia was common in adolescent age group (66%), Osteitis Fibrosa Cystica (OFC) in adult group (36%) while mixed variety in elder group (50%). Similarly OFC was the most common pattern in both genders. Conclusion: In the present study it was concluded that the prevalence of renal osteodystrophy was significantly increased. Secondary hyperparathyroidism (Osteitis Fibrosa Cystica) is the most common pattern of ROD followed by mixed osteodystrophy and adynamic bone disease.

INTRODUCTION: Phosphate binding with sevelamer can ameliorate detrimental histomorphometric changes of bone in chronic renal insufficiency (CRI). Here we explored the effects of sevelamer-HCl treatment on bone strength and structure in experimental CRI. METHODS: Forty-eight 8-week-old rats were assigned to surgical 5/6 nephrectomy (CRI) or renal decapsulation (Sham). After 14 weeks of disease progression, the rats were allocated to untreated and sevelamer-treated (3% in chow) groups for 9 weeks. Then the animals were sacrificed, plasma samples collected, and femora excised for structural analysis (biomechanical testing, quantitative computed tomography). RESULTS: Sevelamer-HCl significantly reduced blood pH, and final creatinine clearance in the CRI groups ranged 30%-50% of that in the Sham group. Final plasma phosphate increased 2.4- to 2.9-fold, and parathyroid hormone 13- to 21-fold in CRI rats, with no difference between sevelamer-treated and untreated animals. In the femoral midshaft, CRI reduced cortical bone mineral density (-3%) and breaking load (-15%) (p

SUMMARY Objective To examine the effect of self-management dietary counselling (SMDC) on adherence to dietary management of hyperphosphatemia among haemodialysis patients. Design An eight-week cluster based randomised control trial. Participants 122 stable adult patients were recruited from an HD unit in Sidon, Lebanon. Study groups were: full intervention (A) (n = 41), partial intervention (B) (n = 41) and control (C) (n = 40). Intervention Group (A) received SMDC, Group (B) received educational games only and Group (C) did not receive any research intervention. Main Outcome Measures Serum phosphorus (P), Calcium Phosphate product (Ca × P) and two questionnaires: patient knowledge (PK) and dietary non-adherence (PDnA) to P reduced diet. Results Group A experienced a significant improvement in mean (± SD) P (6.54 ± 2.05 − 5.4 ± 1.97 mg/dl), Ca × P (58 ± 17 − 49 ± 12), PK scores (50 ± 17 − 69 ± 25%) and PDnA scores (21.4 ± 4.0 − 18.3 ± 2.0). Group B experienced a significant improvement in Ca × P (52 ± 14–45 ± 16). Group C did not experience any significant change post intervention. Conclusion Our findings demonstrate the importance of patient-tailored counselling on serum P management.

Purpose: To find-out causes of dysphagia in an Indian population and to assess whether the cases termed globus actually has some underlying cause. Methods: History elucidation, ENT examination, neurological check up and neuromuscular examination. Barium swallows of esophagus, upper flexible GED scopy, flexible laryngoscopy, X-ray cervical spine. X-ray soft tissue neck lateral view, CXR, CT scan, MRI and diagnostic rigid esophagoscopy. Results: Hypopharyngeal carcinoma (pyriform fossa) 25% (30) and esophagitis, stricture, caustic injury, webs, 25% (30) commonest cause of dysphagia in India. Osteoarthropathy, Diffuse idiopathic skeletal hyperostosis (DISH) 2.5% (2) are significant cause of dysphagia though not common. No Patient was found to have globus hystericus. Conclusion: Osteodystrophy though not a common cause of dysphagia, but should be kept in mind when other apparent causes of it are negated and before diagnosing it as globus hystericus as in our study none of the patients were found to have globus. DOI: http://dx.doi.org/10.3329/bjo.v18i2.11992 Bangladesh J Otorhinolaryngol 2012; 18(2): 145-148

Pseudohypoparathyroidism due to deficient end organ response to parathyroid hormone (PTH) is characterized by hypocalcemia, hyperphosphatemia and increased serum PTH. We report a case of an 8-year-old girl with pseudohypoparathyroidism without features of Albright's hereditary osteodystrophy. The case is of interest as the child on serial follow-up over a period of 2 years developed hypothyroidism. This is a rare feature seen in pseudohypoparathyroidism type1b.

Pseudohypoparathyroidism (PHP) is a rare hereditary disorder having the prevalence of 3.4 per million. It is characterized by symptoms and signs of hypoparathyroidism, typically in association with distinctive skeletal and developmental defects. The features of hypoparathyroidism are due to tissue resistance to the effect of parathyroid hormone (PTH). We will describe a 32-yearold woman who had recurrent convulsion for 16 years, infertility, cataract, psychosis, candidiasis and typical features of Albright’s hereditary osteodystrophy (AHO), which include a round face, short neck, short stature and brachydactyly. Laboratory investigations showed hypocalcemia, hyperphosphatemia with high PTH level. Computed tomography scan of head revealed wide spread calcification in basal ganglia and cerebral hemispheres. X ray of left foot showed short left 4th metatarsal bone. The patient was diagnosed as a case of PHP on the basis of somatic features of AHO with typical biochemical abnormalities and uncontrolled convulsion with combined antiepileptic drugs for 16 years. The unusual features in our case are long delay in clinical diagnosis and absence of family history. She was treated with calcium salt and vitamin D. With this treatment patient’s condition was improved and she experiences no attack of convulsion and carpal spasm. Anticonvulsants were withdrawn gradually. We recommend that hypocalcaemia should be excluded before commencing anticonvulsant therapy in all epileptic patients and those patients whose seizures are refractory to anticonvulsant drugs DOI: http://dx.doi.org/10.3329/jbcps.v29i4.11331 J Bangladesh Coll Phys Surg 2011; 29: 227-230

In chronic kidney disease (CKD), osteodystrophy and arterial calcification often coexist. However, arterial alterations have not been addressed in CKD unaccompanied by evidence of calcification. We investigated the association of phosphate (P) and calcium (Ca) accumulation in calcification-free aortas with CKD-induced osteodystrophy. Aortic accumulation of magnesium (Mg), an inhibitor of calcification, was also examined. Male mice aged 26 weeks with CKD characterized by hyperparathyroidism and hyperphosphatemia (Nx, n = 8) and age-matched healthy male mice (shams, n = 8) were sampled for blood, and thoracic vertebrae and aortas were harvested. Bone structure and chemicals were analyzed by microcomputed tomography and infrared microspectroscopy, respectively, and aortic accumulation of P, Ca, and Mg was evaluated by plasma-atomic emission spectrometry. Volume fractions of cortical and trabecular bones were smaller in Nx than in sham animals (P

Pseudohypoparathyroidism is characterized by hypocalcemia, hyperphosphatemia and hyperparathyroid hormone (PTH)-emia defined by target organ (kidney and bone) unresponsiveness to PTH. Because the clinical symptoms and hypocalcemia appear when the patients are approximately 3 years of age, the clinical features during early infancy remain unknown. An infant female patient had transient renal tubular acidosis (RTA), which improved only with conservative therapy. Thereafter, the patient exhibited the characteristics of Albright’s hereditary osteodystrophy, including short stature, round and puffy face, obesity, and psychomotor retardation. According to the clinical findings of PTH-resistant hypocalcemia, hyperphosphatemia and hyper-PTH-emia, which simultaneously occurred with growth hormone (GH) deficiency and hypothyroidism, the clinical diagnosis of pseudohypoparathyroidism type 1a was made when the patient was 1 year 8 months of age. This is the first report of a patient with pseudohypoparathyroidism who had neonatal RTA. We herein discuss the basic pathogenesis of the coincidental nature of these two problems. This case report might help to elucidate the clinical features of neonatal patients with pseudohypoparathyroidism type 1a.

Background In Belgium and the Netherlands, up to 40% of the children on dialysis are children with immigrant parents of non-Western European origin (non-Western). Concerns exist regarding whether these non-Western patients receive the same quality of care as children with parents of Western European origin (Western). We compared initial dialysis, post-initial treatment, and outcomes between non-Western and Western patients on dialysis. Methods All children, SCOPUS: ar.j, info:eu-repo/semantics/published

Osteoporosis and osteomalacia are, to date, among the most common metabolic diseases in the world. Lately, an association between metabolic bone diseases and chronic liver disease has been increasingly reported, inducing many authors to create a new nosographic entity known as 'hepatic osteodystrophy.' The importance of such a condition is further increased by the morbidity of these two diseases, which greatly reduce the quality of life because of frequent fractures, especially vertebral and femoral neck ones. For this reason, early identification of high-risk patients should be routinely performed by measuring bone mass density. The explanation for the association between bone diseases and chronic liver disease is still uncertain, and involves many factors: from hypogonadism to use of corticosteroid drugs, from genetic factors to interferon therapy. To date, few studies have been conducted, and all with a small number of patients to establish definitive conclusions about the possible treatment, but some evidence is beginning to emerge about the safety and efficacy of bisphosphonates.

This short note illustrates facial and head features found in a stone sculpture of the ancient, Precolumbian period in a temple of the Mayan city of Copan (Honduras). The authors believe that this observation may support paleoanthropological evidence of Paget’s disease of bone, an osteodystrophy described in the Mesoamerican Indian populations before the first millennium A.D.

Chronic kidney disease-mineral and bone disorder (CKD-MBD) is a complex interplay of risk factors, diseases and outcomes. In the last two decades, there has been a steady drift towards definitions depending ever more closely on laboratory abnormalities, which only represent at best possible risk factors for downstream pathology. In the early years of nephrology, especially when the therapeutic agents we had available to combat CKD–MBD were modest, bone and muscle problems were often advanced, and symptomatic, with bone and muscle pain, fractures and myopathy. This ‘old style’ hyperparathyroidism paradigm has become substantially less common now, and we can forget how symptomatic, and how draining of life-quality, CKD-MBD can be. In this chapter, we explore in the main the most feared complication of all, that of a fracture, which not only are dramatically more common in CKD patients, but also have a much heightened mortality over similar fractures but not in a CKD setting.

To study bone mineral content (BMC), bone mineral density (BMD), vitamin D status, and bone mineral variables in patients with chronic nonalcoholic pancreatitis and to determine the relationship between pancreatic dysfunction and these variables.Thirty-one eligible nonalcoholic men with proven chronic pancreatitis and 35 male control subjects were studied. Biochemical data, variables of malabsorption, and BMD of the lumbar spine were evaluated.In patients with chronic pancreatitis, the mean body mass index (BMI) was 18.46 kg/m² and the median 25-hydroxyvitamin D value was 15.5 (range, 5.0 to 52.0) ng/mL. A T-score of less than -2.5 was found in a higher proportion of study patients (9 of 31, 29%) than of control subjects (3 of 35, 9%). BMI correlated significantly with BMC (r = 0.426; P = .017). There was an inverse correlation between stool fat and BMC (r = -0.47; P = .03) in patients with chronic pancreatitis and steatorrhea. There was no significant correlation between serum 25-hydroxyvitamin D or biochemical variables and BMD. Patients with steatorrhea had a significantly lower BMC than did those without steatorrhea, and this difference could not be accounted for by differences in BMI, presence of diabetes, or hypovitaminosis D.Pancreatic osteodystrophy is a novel entity consisting of osteopenia, osteoporosis, and osteomalacia in patients with chronic pancreatitis. The inverse correlation between stool fat and BMC in patients with chronic pancreatitis, the strong positive correlation between BMI and BMC, and the lack of difference in BMC between subjects with vitamin D sufficiency and those with vitamin D deficiency suggest that long-standing malabsorption with attendant chronic undernutrition is the major factor contributing to the changes in BMC.

Bone is a dynamic tissue. Skeletal bone integrity is maintained through bone modeling and remodeling. The mechanisms underlying this bone mass regulation are complex and interrelated. An imbalance in the regulation of bone remodeling through bone resorption and bone formation results in bone loss. Chronic inflammation influences bone mass regulation. Inflammation-related bone disorders share many common mechanisms of bone loss. These mechanisms are ultimately mediated through the uncoupling of bone remodeling. Cachexia, physical inactivity, pro-inflammatory cytokines, as well as iatrogenic factors related to effects of immunosuppression are some of the common mechanisms. Recently, cytokine signaling through the central nervous system has been investigated for its potential role in bone mass dysregulation in inflammatory conditions. Growing research on the molecular mechanisms involved in inflammation-induced bone loss may lead to more selective therapeutic targeting of these pathological signaling pathways.

Patients with cirrhosis are more prone to develop metabolic bone disease. Scanty literature data are available on osteodystrophy in patients from India with noncholestatic liver diseases. Patients diagnosed with cirrhosis were prospectively evaluated for bone mineral density (BMD) as measured by dual-energy X-ray absorptiometry at the femoral neck, lumbar spine, and left forearm (distal radius). Correlation of BMD with age, sex, etiology of cirrhosis, Child’s class, serum bilirubin, alkaline phosphatase (ALP), albumin, calcium, phosphate, 25-hydroxyvitamin D (25(OH)D), and parathyroid hormone (PTH) was studied. The study group comprised 115 cirrhotic patients (107 males and 8 females). Etiology of cirrhosis was alcohol in 67 (58.2%) and viral in 48 (41.7%). Hepatitis B was diagnosed in 29 (25.2%) and hepatitis C in 19 (16.5%). Mean age was 49 (± 5.5) years. Prevalence of osteodystrophy was significantly higher in males than in females; 97.1% and 75% respectively (P = .038). Both alcoholic and viral groups had similar baseline characteristics except albumin levels. Child’s class was B in 72 patients and C in 43. Low BMD was present in 97% of patients with alcoholic cirrhosis and 93.7% with viral cirrhosis (P > .05). Low BMD was present at the femoral neck in 80.8% of patients, lumbar spine in 77.3%, and forearm in 59.9%. PTH correlated negatively with BMD. Osteodystrophy is common in alcoholic and viral cirrhosis patients.

Resumen: El pseudohipoparatiroidismo (PHP) comprende un grupo heterogéneo de enfermedades endocrinológicas que se caracterizan por la existencia de hipocalcemia, hiperfosfatemia y resistencia tisular a la hormona paratiroidea. Se distinguen diferentes formas de PHP. El PHP-Ia es la forma más frecuente y asocia resistencia hormonal múltiple, signos clínicos de osteodistrofia hereditaria de Albright (OHA) y mutaciones en el gen GNAS codificador de la proteína Gsα. El pseudoPHP (PPHP) asocia igualmente mutaciones en el gen GNAS pero cursa con OHA aislada sin anomalías endocrinas. Se presenta una familia con madre afecta de PPHP y dos hijas con PHP-Ia que comparten la misma mutación inactivadora en heterocigosis en el gen GNAS (Asn264LysfsX35). Se discute la diferente expresividad clínica así como el modelo de herencia dominante con impronta genética en el que el fenotipo de la descendencia está deteminado por el sexo del progenitor afecto. Abstract: Pseudohypoparathyroidism (PHP) is a heterogeneous group of endocrine diseases characterised by hypocalcaemia, hyperphosphataemia and resistance to PTH. There are different forms of PHP. PHP-Ia is the most frequent form and shows multi-hormonal resistance, GNAS (Gsα) mutations and signs of Albright́s hereditary osteodystrophy (AHO). PseudoPHP (PPHP) have isolated AHO without hormonal resistance and it is also caused by GNAS mutations. We present a family that share the same inactivating GNAS mutation (Asn264LysfsX35); the mother being affected with PPHP and the two daughters with PHP-Ia. We discuss the different clinical phenotypes and the dominant mode of inheritance with genetic imprinting where the phenotype of the offspring depends on the sex of the parent affected.

The authors describe a 6 year old girl who initially presented with limping due to intraarticular ossification of left knee joint but later developed carpopedal spasms. She had Albright's hereditary osteodystrophy phenotype with hypocalcemia and hyperphosphatemia with elevated parathyroid hormone. She was diagnosed to have pseudohypoparathyroidism 1a (PHP1a) with heterotopic intraarticular ossification. This case emphasizes the need for evaluation of PHP in patients with intraarticular ossification to facilitate early diagnosis of PHP.

Abnormalities in bone morphology that develop secondary to chronic kidney disease are defined as renal osteodystrophy and are identified by bone biopsy. As systematic and sequential bone biopsy is not practicable on a large number of patients, various chemical bone markers are commonly used to detect the bone remodeling status in chronic kidney disease and to grade bone disease in the clinical setting. Recent literature has considered the effect of absolute levels of parathyroid hormone (PTH) on clinical outcomes and not the measurement of their change over time, the PTH variability. In a retrospective observational study, we examined PTH variability parameters in a group of hemodialysis patients as independent risk factors for high vs. low turnover osteopathy, and investigated their usefulness with respect to commonly used markers of renal osteodystrophy. The study was conducted on 90 chronic hemodialysis patients undergoing regular treatment at the same dialysis centre (Catanzaro, Italy) with standard bicarbonate dialysis. Patients were classified into either high or medium-low turnover osteopathy for the diagnosis based on renal osteodystrophy using the following criteria: PTH ≥ 400 pg/mL associated with bone ALP ≥ 20 ng/mL. We used a regression-based measurement of PTH variability, which was characterized by different parameters: PTH-Res-SD, PTH-Slope, PTH-Intercept, PTH-Abs-Var, and PTH-Res-SD. In our analysis, these parameters of PTH variability were demonstrated to be good independent predictive factors for high turnover osteodystrophy, and they had a greater sensitivity than the use of a single and/or mean PTH measurements in renal osteodystrophy classification.

Aim To assess the natural history and impact of the secondary bone disease observed in patients with Mucolipidosis II and III.

PURPOSE To describe the clinical and radiologic features of orbital involvement in craniofacial brown tumors and to compare the rate of brown tumors in primary and secondary hyperparathyroidism. METHODS A retrospective hospital-based study of 115 patients with chronic kidney disease and secondary hyperparathyroidism and 34 with primary hyperparathyroidism was conducted. Laboratory results such as serum levels of alkaline phosphatase, calcium, phosphorus, and parathyroid hormone were recorded. Demographic data (age, sex, duration of disease) and image findings (bone scan scintigraphy, skull and long bone x-rays, CT) were also obtained. The main outcome measures were analysis of clinical, biochemical, and radiologic findings of all patients. RESULTS Of the 115 patients with chronic kidney disease, 10 (8.7%) had brown tumors in different bones of the skeleton. Five patients had lesions in the craniofacial bones. The maxilla, mandible, maxillary sinus, and nasal cavity were the most affected sites. The orbit was involved in 2 patients with lesions arising in the maxillary and ethmoid sinuses. One patient had facial leontiasis. All patients with brown tumors had extremely high levels of parathyroid hormone (>1,000 pg/ml, normal values 10-69 pg/ml) and alkaline phosphatase (>400 U/l, normal values 65-300 U/l). The mean serum levels of phosphorus and calcium were not abnormal among the patients with brown tumors. Age and time of renal failure were similar for patients with and without brown tumors. Among the patients with primary hyperparathyroidism, only 2 (5.8%) had brown tumors, and in just 1, the lesion was localized in the craniofacial skeleton. A 2-tailed Z test applied to compare the proportion of occurrence of brown tumors in the 2 groups revealed that the difference at the 90% of confidence level was not significant. CONCLUSIONS Brown tumors are equally found in secondary and primary hyperparathyroidism. Craniofacial brown tumors involve the orbit, usually because of the osteodystrophy process that involves the maxilla and paranasal sinuses. The lesions do not necessarily need to be excised and may regress spontaneously after the control of hyperparathyroidism.

Chronic kidney disease (CKD) is a worldwide health problem with increasing prevalence and poor outcomes, including severe cardiovascular disease and renal osteodystrophy. With advances in medical treatment, patients with CKD are living longer and require oral care. The aim of this study is to determine the effects of CKD and dietary phosphate on mandibular bone structure using a uremic mouse model.Uremia (U) was induced in female dilute brown agouti/2 mice by partial renal ablation. Uremic mice received a normal-phosphate (NP) or a high-phosphate (HP) diet. sham surgeries were performed in a control group of mice; half received an NP diet, and the other half was fed an HP diet. At termination, animals were sacrificed, and mandibles were collected for microcomputed tomography (micro-CT) and histologic analysis.Sera levels of blood urea nitrogen, parathyroid hormone, and alkaline phosphatase were significantly increased in U/NP and U/HP mice versus sham controls, whereas serum calcium was increased in the U/HP group, and no differences were noted in serum phosphate levels among groups. Micro-CT analyses revealed a significant reduction in cortical bone thickness and an increase in trabecular thickness and trabecular bone volume/tissue volume in U/NP and U/HP groups compared to the sham/NP group. A significant reduction in cortical bone thickness was also found in the sham/HP group versus the sham/NP group. Histologic evaluation confirmed increased trabeculation in the U groups.CKD in mice, especially under conditions of HP feeding, results in marked effects on alveolar bone homeostasis.

Background/Aims: Dual energy X-ray absorptiometry (DEXA) scanning is used to assess bone mineral content and diagnose osteoporosis. We had noted anecdotal cases of patients attending for DEXA scanning following recent ingestion of barium-containing radiocontrast media, resulting in spuriously increased bone mineral content. Lanthanum carbonate is prescribed to chronic kidney disease patients as a non-calcium-containing phosphate binder, and as lanthanum is denser than barium, we wondered whether this could affect DEXA scan bone mineral estimations. Methods: DEXA scan records were reviewed from a cohort of 169 chronic dialysis patients, 24 (14%) of whom were prescribed lanthanum carbonate. Results: Estimation of segmental bone mineral content by DEXA was similar between the groups for the arms, legs, ribs, thoracic spine, hips and pelvis, apart from the lumbar spine for which it was greater for the lanthanum group (1.05 ± 0.05 vs. 0.98 ± 0.01 gm/cm2, p < 0.05). Similarly, T and Z scores were higher in the lanthanum group for the lumbar spine (T score: –0.2 ± 0.4 vs. –0.92 ± 0.1; Z score: 0.68 ± 0.4 vs. –0.01 ± 0.1; p < 0.05), but not different for the hip (T score: –1.108 ± 0.28 vs. –0.966 ± 0.09; Z: score –0.49 ± 0.25 vs. –0.3 ± 0.01). Conclusion: DEXA scanning in patients prescribed lanthanum can lead to an erroneously high estimation of bone mineral content in areas of the skeleton adjacent to the bowel when the electron beam meets lanthanum.

The relationship between bone-resorbing cells, assessed by the presence of tartrate-resistant acid phosphatases (TRAP) and morphologic indices of bone resorption, was determined in 29 osteoporotic patients (14 postmenopausal females and 15 males) and 15 dialyzed patients. The number of TRAP-positive cells per unit of cancellous bone area (N.Oc/B.Ar) was higher in dialyzed patients than in those with osteoporosis (16.8 +/- 15.3 versus 4.95 +/- 2.86, p less than 0.05). The amount of bone resorbed at the basic multicellular unit level was estimated by calculating eroded area containing TRAP cells per bone area (E.Ar+/BA). This novel parameter was similar in dialyzed and in osteoporotic patients (41,700 +/- 28,400 versus 32,300 +/- 24,600). In contrast, trabecular spacing (Tb.Sp) was identical in both metabolic bone diseases. Trabecular width (169 +/- 38 versus 127 +/- 32 microns, p less than 0.05) and bone area were higher in dialyzed than in osteoporotic patients. N.Oc/B.Ar was significantly related to E.Ar+/BA in dialyzed (r = 0.76, p less than 0.05) but not in osteoporotic patients. Tb.Sp was significantly correlated to N.Oc/B.Ar and to the number of TRAP-positive cell nuclei per B.Ar (r = 0.44, p less than 0.05) in osteoporotic but not in dialyzed patients. This last result shows that in overt osteoporosis with thin trabeculae, trabecular spacing is related to the number of resorbing cells. In contrast, the spacing of thick trabeculae in dialysis osteodystrophy is not dependent on the number of osteoclasts.

Albright's hereditary osteodystrophy (AHO) is an inherited disorder and results from heterozygous loss of function mutation within the human G (s)α gene (GNAS1). AHO appears in two phenotypes, that may occur within the same family. Pseudohypoparathyroidism type Ia (PHP Ia) comprises the clinical features of AHO associated with parathyroid hormone (PTH) resistance while pseudo-pseudohypoparathyroidism (PPHP) includes AHO features without PTH resistance. In the present study we report a mother and a daughter with PPHP and PHP Ia respectively. The 13 exons of GNAS1 were analysed by PCR and direct sequencing. We identified a heterozygous missense mutation in exon 1. This novel mutation results in a stop at codon 35 and a truncated non-functional GNAS1 protein.

Osteodystrophy is one of the long-term haemodialysis complications. In diabetic end stage renal failure patients, it mainly occurs as an aplastic or low-turnover bone disease due to their low serum intact parathyroid hormone (iPTH) levels. The aim of the present study is to evaluate intact PTH level in in Egyptian type 2 diabetics with chronic hemodialysis and its relation to glycaemic control .patients. 140 Egyptian patients, their mean age was 60.4 ± 10.6 years were evaluated. They were maintained on regular hemodialysis (HD); 3 times/week, and the patients were divided into two groups according to primary kidney disease, diabetic (98 patients) and non-diabetic (42 patients) groups. Diabetic group was furtherly subdivided according to glycated hemoglobin to controlled (32 patients) and non-controlled diabetics (66 patients). Intact parathyroid hormone (iPTH), glycated hemoglobin (HbA1c), serum bone specific alkaline phosphatase, Albumin, Glucose, calcium, phosphorus and magnesium were estimated. Urea reduction ratio (URR) was estimated to evaluate the hemodialysis adequacy. The diabetic group had significantly lower values of iPTH and serum magnesium than non-diabetic group (p < 0.03 and p < 0.001 respectively). The uncontrolled diabetics had significantly lower values of iPTH, serum magnesium and serum albumin (p < 0.002, p < 0.002& p < 0.03 respectively) than the controlled group. The serum HbA1c levels were strongly correlated with the serum iPTH levels (P < 0.003). intact PTH was lower in diabetic hemodialysis patients; also, glycaemic control was associated with higher PTH levels.

The study investigated whether the type of bone disease management (aggressive versus conventional) had an impact on clinical outcomes, namely bone health measures (e.g., biointact parathyroid hormone [BiPTH], serum corrected calcium [cCa] level, serum phosphorus [phos] level, and corrected calcium-phosphorus product [cCaPO(4)]).Retrospective chart review of 173 closed medical records of maintenance hemodialysis patients on thrice-weekly therapy from January 1, 2005, through December 31, 2005. Two Conventional Management (i.e., control group) and three Aggressive Management (i.e., treatment group) dialysis facilities were enrolled.There was a significant interaction for group assignment and BiPTH levels (F = 4.12, P = .01), with the Aggressive Group trending toward lower BiPTH levels than the Conventional Group. The Conventional Group experienced a significantly lower mean annualized serum cCa level (F = 8.85, P = .003), and used non-calcium-based binders significantly more (P.0005) than the Aggressive Group. In terms of serum phos level, the Aggressive Group had a significantly lower (F = 2.73, P = .05) value than the Conventional Group. No significant differences were reported for cCaPO(4) product (F = 1.87, P = .17). The percentage of the total sample that achieved target range for all bone health measures included 29.8% (n = 50).The study demonstrated that aggressive bone disease management appears to be as effective as traditional interventions in the treatment of mineral and bone metabolism disorders in chronic kidney disease.

A 58-year-old woman with a surgical history of jejunoileal bypass in 1980 for weight reduction sought medical attention with multiple complaints. The patient had not been taking any nutritional supplements since her bypass surgery, 26 years previously. She was found to have osteomalacia, chronic diarrhea, secondary hyperparathyroidism, and hyperoxaluria with a frequent history of nephrolithiasis. Because of her severe osteodystrophy and metabolic complications, reversal of her jejunoileal bypass was recommended. Reversal of the jejunoileal bypass with a sleeve gastrectomy was performed. Laparotomy revealed brown discoloration of the entire alimentary limb with atrophy of the bypassed intestinal limb. Histologic examination of the resected small bowel demonstrated brown pigment deposits within smooth muscle cells of the bowel wall. The pigment stained positive with Fontana-Masson most likely representing lipofuscin. We report a case of brown bowel syndrome complicating jejunoileal bypass, the first case reported in the literature to the best of our knowledge.

Modern strategies to prevent secondary hyperparathyroidism (SHPT) in chronic kidney disease (CKD) patients give great relevance to vitamin D replacement therapy. However, a sound approach to treatment requires taking into account many factors, including stage of CKD, underlying renal disorder, levels of circulating PTH, bone status, vitamin D deposits, and serum calcium (Ca) and phosphate (P) levels. The aim of vitamin D replacement therapy should be to prevent SHPT from the early stages of CKD, because once parathyroid hyperplasia and osteodystrophy develop, they cannot be completely reverted. The therapeutic strategies for SHPT are now changing. The availability of VDRAs allows inhibition of parathyroid glands with less effect on calcium and phosphate levels, and perhaps reduces the mortality of dialysis patients. Actual objectives for treating CKD patients with new generation VDRAs are to retain or amplify the effects of calcitriol on PTH suppression, with no effects on serum Ca and P levels. Paricalcitol is such a new VDRA with minimal impact on serum Ca and P levels. Since cardiovascular disease is the leading cause of morbidity and mortality in dialysis patients, these data suggest that the beneficial effect associated with paricalcitol injection on patient survival is at least partially related to its effect on the cardiovascular system.

Early diagnosis of persistent hyperparathyroidism (HP) following kidney transplantation may prevent worsening of osteodystrophy and potential damage to the graft. We evaluated the utility of collagen pyridinoline (PYD) and deoxypyridinoline (DPD) urinary cross-links beyond the common HP markers to evaluate 70 selected stable recipients between 1997 and 2006 who were divided into 2 group depending on the immunosuppressive protocol. All patients showed elevated levels of urinary cross-links even though calcemia and phosphoremia values were normal. Their mean creatinine level was slightly increased. Data were assessed as mean values +/- SD. All variables underwent a correlation matrix analysis and a stepwise regression, with posttransplant intact parathyroid hormone (iPTH) as the dependent variable and other variables as regressors. A statistically significant correlation was observed between PYD and alkaline phosphatase (ALP; P = .0026, r = .41); PYD and DPD (P = .015, r = .34); pre- and posttransplant iPTH (P = .024, r = .31); and creatinine and ALP (P = .024, r = .31). Taking the groups separately, there were significant correlations between PYD and ALP (P = .0076, r = .42); PYD and DPD (P = .017, r = .38); ALP and posttransplant iPTH (P = .038, r = .33); osteocalcin (OC) and posttransplant iPTH (P = .048, r = .32); and pre- and posttransplant iPTH (P = .019, r = .37) among subjects in the first group, whereas subjects in the second group showed a correlation between posttransplant iPTH and age at transplantation (P = .032, r = .61). In conclusion, we showed that urinary cross-links may be helpful to reveal bone resorption in kidney recipients when usual bone metabolism parameters do not demonstrate hyperparathyroidism.

Aluminum related osteodystrophy is the most important manifestation of trace metal toxicity related to degenerative diseases of the skeleton. Aluminum overload occurs in chronic renal failure patients on hemodialysis treatment and results from transfer from dialysis solutions and from oral intake of aluminum containing phosphate binding gels. Laboratory diagnosis involves serum and bone analysis and bone staining for aluminum. A challenge test with desferrioxamine also aids in the diagnosis. Electrothermal atomic absorption spectrometry is widely used for aluminum detection. Guidelines for toxic concentrations of aluminum have been established.

Spontaneous fractures occur in seemingly normal bone with no apparent blunt-force trauma. Spontaneous fracture occurs primarily in two distinct groups of patients: the very active young and the elderly. Researchers and clinicians have used several terms interchangeably for spontaneous fracture, including pathologic fracture, fragility fracture, compression fracture, or fatigue or insufficiency fracture. Among the most common causes of spontaneous fracture are osteoporosis (calcium deficiency and corticosteroid-induced), malignancy, overexposure to vitamin A, periprosthetic weakening, Brucellosis, cerebral palsy (especially in children), and osteodystrophy because of chronic renal failure. Preliminary research observations indicate that spontaneous fracture may be a rare adverse outcome associated with bisphosphonates.

In chronic renal failure several factors affect bone homeostasis leading to the development of renal osteodystrophy. Common calcitropic hormone derangements in renal failure play a central role in bone structure and mineral defects, which in turn accompany osteodystrophy frequently resulting in low bone mineral density (BMD) values. However, patients with end-stage renal disease (ESRD) suffer from several comorbidities, which may partly account for renal bone disease lesions. Hypogonadism in particular accompanies chronic renal failure frequently and exerts an additive effect on bone loss potential. Sex hormones contribute to the equilibrium of osteotropic hormones and cytokines, exerting a protective action on bone tissue. Estrogens have a regulatory effect on bone metabolism in women with renal failure as well. Hypogonadal ESRD women experience a higher bone turnover and more significant bone mass decrements than ESRD women with relatively normal hormone profile and menstrual habits. Female hemodialysis patients have lower BMD values than male patients on average, probably because of menstrual cycle irregularities. However, hypogonadal ESRD men may also experience bone mineral deficits and the severity of hypogonadism may correlate to their bone mineral status. Hormone replacement therapy (HRT) appears to reverse bone mineral loss to some extent in both sexes. In conclusion hypogonadism in renal failure contributes to the bone structure and mineral defects as well as the low-energy fracture risk, reflected in BMD measurements. HRT in ESRD patients should therefore not be overlooked in these patients in the face of their significant comorbidities.

Phosphorus is one of the important factors that accelerate the progression of chronic kidney disease. Phosphorus restriction or phosphate binders have been reported to have the ability to prevent the progression of chronic kidney disease. FGF23 is a circulating factor that regulates renal phosphorus reabsorption and 1 alpha-hydroxylase activity. We focused on the phosphaturic activity of FGF23 and investigated whether a pharmacological dose of FGF23 is beneficial to the progression of renal insufficiency in uremic rats. To this end, we administered one of the mutant FGF23 expression plasmids into irreversible Thy1 rats. Chronic renal failure rats were established by intravenous injection of anti-rat CD90 (Thy1.1) monoclonal antibody to unilaterally nephrectomized Wistar rats. The rats were then intravenously injected every 2 wk with a naked DNA solution containing 10 microg of MOCK vector or a mutant FGF23 expression plasmid for 13 wk. Renal function was assessed biochemically and histopathologically. Mutant FGF23 significantly decreased serum creatinine and serum urea nitrogen. The marked glomerular sclerosis observed in uremic rats receiving the MOCK vector was ameliorated in rats treated with mutant FGF23. However, mutant FGF23 not only significantly decreased serum 1,25(OH)(2)D and calcium but also aggravated high-turnover renal osteodystrophy from extremely high levels of PTH. These results might be a result of the mechanisms of FGF23 such as phosphaturic activity and lowering the level of 1,25(OH)(2)D. In conclusion, mutant FGF23 prevented the progression of chronic renal failure by regulating serum phosphorus but aggravated renal osteodystrophy from the lowered levels of 1,25(OH)(2)D.