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Parathormone is a key polypeptide hormone controlling bone remodeling by influencing calcium, phosphorus, and vitamin D homeostasis in mammalian body. This report describes unusual presentation of osteodystrophy causing facial hyperostosis due to nutritional secondary hyperparathyroidism in a puppy. A female Labrador Retriever dog aged 5 months was presented with progressive bilaterally symmetrical swelling on facial region, hypersalivation, and reduced growth rate. Excessive meat intake in daily ration since weaning was reported. Clinical examination revealed dyspnoea, open mouth breathing, epiphora, excessive nasal secretions, tachycardia, pale mucous membranes, debility, loosely attached teeth, and pigmented oral mucosa of the upper jaw. Microcytic anemia, lymphocytosis, eosinophilia, monocytopenia, hypoproteinemia with hypoglobulinemia, hyperalbuminemia, hypocalcemia, hyperphosphatemia, and decreased Ca:P ratio were evident in the hemato-biochemical study. Lateral radiographic view of the head revealed hyperostosis of the facial bones with irregularly arranged teeth on the upper jaw. Nutritional secondary hyperparathyroidism–induced facial osteodystrophy was diagnosed in the animal based on the history and other supporting clinical evidence. The animal was treated with a protocol extending for 4 weeks using calcium, calcitriol, essential minerals, vitamins, and steroids. The animal showed considerable improvement on day 14 and regained normal facial architecture by day 28 of the therapy.

BACKGROUND: From 1980s to the new millennium, the number of patients surviving with end stage renal disease (ESRD) has increased by 3 fold. This is driven by early detection of primordial and primary risk factors, state of the art renal replacement therapy and ease of public access to healthcare. Renal osteodystrophy (RO) is a metabolic bone disease causing significant morbidity in patients with ESRD, in particular fragility fractures. In this case series, we present the surgical management of 3 ESRD patients with pathological fractures of the neck of femur (NOF) and surgical treatment (parathyroidectomy) of tertiary hyperparathyroidism of ESRD patients in the same surgical setting. Up to date there has been no reports on bipolar hemiarthroplasty and total parathyroidectomy implemented in the same operative setting. METHODS: We present 3 cases, 2 males and a female with an average age of 48 years. All patients presented with no trauma or minimal trauma. With high index of suspicion and after confirming the diagnosis with advanced imaging, the patients underwent cemented modular hemiarthroplasty with posterior approach. Parathyroidectomy was sequentially performed to address the tertiary hyperparathyroidism at the same setting. We followed them for 48 months. RESULTS: At 48-month follow up, all the patients were at their pre-morbid ambulatory status and there were no major complications. They did not need any revision surgery or re-operation either for the hemiarthroplasty surgery or the parathyroidectomy during the follow up period. CONCLUSION: To avoid diagnostic pitfalls in this group of patients we recommend MRIs of both hips in patients complaining of unilateral hip pain even when the roentgenograms are clear of fractures. Total parathyroidectomy at the same setting with the bipolar hemi-arthroplasty is a safe combination. This reduces the anaesthesia risk, the recovery time as well as the equilibrium time for calcium homeostasis.

Pseudohypoparathyroidism (PHP), characterized by multihormone resistance and Albright’s hereditary osteodystrophy (AHO), is caused by GNAS mutations. Whole or partial gene deletions are rare. All disorders due to inactivating mutations of the GNAS gene are now classified as “inactivating PTH/PTHrP signaling disorder type 2” (iPPSD2). This study reports a family harboring a large GNAS gene deletion in order to improve the knowledge of genotype–phenotype correlation of this disease. An 18-year-old man with severe diffuse soft ossifications and multihormone resistance underwent to clinical, biochemical, radiological, and genetic studies. A review of the literature of other cases of iPPSD2 due to GNAS large deletions was performed focusing on clinical and biochemical features. The proband presented signs of hypocalcemia and marked AHO features. Laboratory tests revealed hypocalcemia, high levels of serum phosphate, PTH, TSH, and calcitonin despite therapy with calcium carbonate, calcitriol, and levothyroxine. Diffuse soft tissue ossifications and brain calcifications were shown by radiological exams. Family history was remarkable for hypocalcemia, neurocognitive impairment, and cerebral calcifications in his brother and AHO features in the maternal grandfather. The proband’s mother showed short stature, whereas physical examination of the father was unremarkable. Genetic analysis of the GNAS gene revealed an unreported large deletion encompassing exons 1–7 in the proband, brother, and mother. By reviewing the literature, only six other cases were described. We report a kindred harboring a large GNAS deletion. A genotype–phenotype correlation was observed in term of severity of tissue ossifications in the siblings but not in the mother.

Osteodystrophy is a frequent complication in primary sclerosing cholangitis (PSC). The aim was to test the feasibility of vertebral bone diffusion-weighted imaging (DWI) in routine liver MRI for detection of osteoporosis using dual-energy X-ray absorptiometry (DXA) as gold standard. Forty PSC patients (50 ± 12.6 years) and ten controls (49.5 ± 13.0 years) were scanned using a DWI spin echo echo-planar sequence (b-factors 0–800 s/mm2) on a 3-T MRI system and DXA (76 kVp). The apparent diffusion coefficient (ADC) and T-score were correlated to laboratory and clinical details using Pearson correlation. In DXA-diagnosed osteoporosis (n = 3) and osteopenia (n = 12), the mean ADC was decreased (0.26 ± 0.03 and 0.30 ± 0.07 × 10−3 mm2/s) compared to patients with normal DXA scan results (n = 25; 0.32 ± 0.06 × 10−3 mm2/s). No significant correlation of the ADC and T-score (r = 0.24; p = 0.13) was found, but the T-score correlated significantly to disease duration (r = −0.33; p = 0.04). In patients with prednisolone therapy (n = 7), the DXA T-score was significantly lower (−1.46 ± 0.49 vs. −0.16 ± 0.23; p = 0.03). Diffusion-weighted MRI of the vertebral spine is a feasible technic to detect diffusion alterations caused by osteoporosis but lacks diagnostic capacities for diagnosing minor reductions of the bone mineral density detected by DXA.

Diabetes and osteoporosis are rapidly growing diseases. The link between the high fracture incidence in diabetes as compared with the non-diabetic state has recently been recognized. While this review cannot cover every aspect of diabetic osteodystrophy, it attempts to incorporate current information from the First International Symposium on Diabetes and Bone presentations in Rome in 2014. Diabetes and osteoporosis are fast-growing diseases in the western world and are becoming a major problem in the emerging economic nations. Aging of populations worldwide will be responsible for an increased risk in the incidence of osteoporosis and diabetes. Furthermore, the economic burden due to complications of these diseases is enormous and will continue to increase unless public awareness of these diseases, the curbing of obesity, and cost-effective measures are instituted. The link between diabetes and fractures being more common in diabetics than non-diabetics has been widely recognized. At the same time, many questions remain regarding the underlying mechanisms for greater bone fragility in diabetic patients and the best approach to risk assessment and treatment to prevent fractures. Although it cannot cover every aspect of diabetic osteodystrophy, this review will attempt to incorporate current information particularly from the First International Symposium on Diabetes and Bone presentations in Rome in November 2014.

Interstitial deletions of the long arm of chromosome 20 are rarely reported in the literature. We report a 2-year-old child with a 2.6 Mb deletion of 20q13.32-q13.33, detected by microarray-based comparative genomic hybridization, who presented with poor growth, feeding difficulties, abnormal subcutaneous fat distribution with the lack of adipose tissue on clinical examination, facial dysmorphism and low bone mass. This report adds to rare publications describing constitutional aberrations of chromosome 20q, and adds further evidence to the fact that deletion of the GNAS complex may not always be associated with an Albright's hereditary osteodystrophy phenotype as described previously.

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.

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

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.

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.

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.

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.

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.

Renal osteodystrophy (ROD) develops early in the course of chronic kidney disease (CKD). With improving patient survival it's importance and relevance has increased. The last published bone biopsy data in children prior to renal replacement therapy (RRT) was in 1982, which demonstrated abnormal histology in all patients with a glomerular filtration rate (GFR)20 ml/min per 1.73 m(2). Studies investigating the relationship between bone histology and parathyroid hormone levels (PTH) and/or growth in children with CKD are few (seven). These were mostly undertaken in patients already initiated on RRT-dialysis. We investigated the presence of ROD in children at the commencement of RRT and to investigate any relationship between histology, growth and PTH levels. Following double tetracycline labelling, bone biopsies were taken from patients at the time of RRT surgery. Histological classification was based on the newly proposed turnover/mineralisation/volume (TMV) system. Eleven patients underwent bone biopsy. Patients were followed for an average of 1.1 years (0.5-1.8) prior to biopsy over an average of eight clinic visits (3-14), when routine biochemical data were collected. Time-integrated median calcium, phosphate and PTH levels were calculated. PTH levels were within the normal range in two patients with low turnover, 1.1-1.4 times the upper limit of normal (ULN) in three with mixed osteodystrophy and2.9 times the ULN in four patients with high bone turnover. There was no relationship between bone turnover and growth. The presence of ROD was universal in these children with severe CKD. Low bone turnover was associated with normal-range mean PTH levels, and high bone turnover occurred at lower PTH levels than current guidelines would suggest.

More than 50% of cancer patients survive for more than 5 years, owing to modern and effective treatment. Therefore, long-term sequelae of treatment are more frequently seen than in the past. Such effects on normal tissue may both mimic and obscure tumor recurrences. Besides the direct consequences of surgery, tissue damage due to radiation or chemotherapy frequently cause problems in differential diagnosis. Among the numerous sequelae of radiotherapy, the most prominent are disturbance of the blood-brain barrier, radiation pneumonitis, osteodystrophy and osteoradionecrosis, fatty changes of bone marrow, or increased radiodensity of breast parenchyma. Chemotherapy may cause, e.g., diffuse abnormalities of white matter, pneumonitis and lung fibrosis, cardiomyopathy, or diffuse and patchy changes in bone marrow signals in MRI. The most devastating long-term complications are secondary cancers and leukemia induced by both radiotherapy and chemotherapy.

Renal hyperparathyroidism (rHPT) almost inevitably develops in pediatric patients with end-stage chronic kidney disease (CKD) and may require parathyroidectomy (PTX) despite intensified conservative therapy. Long-term duration of uncontrolled rHPT may result in disabling osteodystrophy and vascular calcifications. Only a few reports on children undergoing PTX for rHPT are available and mainly consist of case reports with short follow-up periods. To study this entity, we analyzed the course of 23 pediatic patients who underwent PTX for rHPT. Twenty-three patients with a mean age of 15 years and who underwent PTX for rHPT between 1986 and 2006 were evaluated. Surgical indications and techniques, specific postoperative management, and follow-up courses are described. Preoperative mean serum (s-) calcium was 2.7 ± 0.05 mmol/L (normal range = 2.2–2.7 mmol/L); s-phosphate was 1.8 ± 0.1 mmol/L (normal range = 0.8–1.6 mmol/L), and mean intact parathyroid hormone (PTH) level was 1240.1 ± 160.1 pg/ml (normal range = 11–65 pg/ml). Twenty-one patients underwent initial PTX and two patients underwent reoperative PTX. Total PTX with parathyroid autotransplantation (AT) was performed in 18 patients. In three patients less than four parathyroid glands were identified and no AT was performed consecutively. Postoperatively, no complications with respect to bleeding or vocal cord damage were recorded. The postoperative values of s-calcium, s-phosphate, and PTH decreased to or below normal range (s-calcium = 2.0 ± 0.1 mmol/L, s-phosphate = 1.2 ± 0.1 mmol/L, PTH = 50.1 ± 11.2 pg/ml). All 15 children below the age of 15 years required calcium intravenously. Follow-up was obtained in all patients 69.6 ± 11.4 months after PTX. Bone pain resolved in all previously symptomatic patients. S-calcium was 2.2 ± 0.2 mmol/L, s-phosphate was 1.4 ± 0.3 mmol/L, and PTH was 90.2 ± 21.5 pg/ml. No patient required repeated parathyroid autografting, and only one underwent an explantation of his AT six years after initial PTX. Total PTX with AT in pediatric patients with rHPT is a safe and effective procedure. It should be considered if rHPT is refractory to conservative treatment, in view of the risk of potentially lethal vascular calcifications developing in the majority of adults with childhood onset of CKD.

Chronic Kidney Disease (CKD) is commonly associated with alterations in bone and mineral metabolism (renal osteodystrophy). To date, bone biopsy remains the gold standard for the diagnosis and classification of the various types of renal osteodystrophy, namely: osteitis fibrosa, mixed uremic osteodystrophy, osteomalacia, aplastic and adynamic bone disease. However, due to its invasive nature and the fact that it is quite expensive, there has been a clamor for a search for other tests. Traditionally, the level of parathyroid hormone (PTH) has been considered a surrogate of bone turnover. At this time, the search continues for a specific and sensitive biochemical marker for monitoring bone turnover in CKD., e.g., alkaline phosphatase, osteocalcin, collagen degradation products, etc. In this chapter, we also present the common radiographic findings that are commonly seen in patients with renal osteodystrophy. Other radiographic techniques such as, dual energy x-ray absorptiometry (DEXA) and deferoxamine challenge test (DFO) are also briefly discussed.

One of the major complications that arise as a result of chronic kidney disease is that of ‘renal osteodystrophy.’ It is believed to be a multifactorial disorder of altered bone modeling. Bone biopsy occupies a central role in the differentiation of the various kinds of renal osteodystrophy based on histological findings. However, due to its limitations of being a rather invasive and costly procedure, it is performed rather infrequently. Therefore, scientists started to focus on alternative measures of classifying the various types, e.g., the parathyroid hormone (PTH). PTH has been used as an indicator of bone turnover, thereby dividing the diseases into those of high turnover and low turnover. To further our understanding of this particular disease entity, a unified definition and classification was formulated and adopted by well-renowned experts from both local and international scenes, and this is presented in some detail in this chapter. It is hoped, that such unification will enhance communication, facilitate clinical decision making, and promote the evolution of evidence-based clinical practice guidelines worldwide. (2)

Childhood and adolescence are crucial times for the development of a healthy skeletal and cardiovascular system. Disordered mineral and bone metabolism accompany chronic kidney disease (CKD) and present significant obstacles to optimal bone strength, final adult height, and cardiovascular health. Decreased activity of renal 1 alpha hydroxylase results in decreased intestinal calcium absorption, increased serum parathyroid hormone levels, and high-turnover renal osteodystrophy, with subsequent growth failure. Simultaneously, phosphorus retention exacerbates secondary hyperparathyroidism, and elevated levels contribute to cardiovascular disease. Treatment of hyperphosphatemia and secondary hyperparathyroidism improves growth and high-turnover bone disease. However, target ranges for serum calcium, phosphorus, and parathyroid hormone (PTH) levels vary according to stage of CKD. Since over-treatment may result in adynamic bone disease, growth failure, hypercalcemia, and progression of cardiovascular calcifications, therapy must be carefully adjusted to maintain optimal serum biochemical parameters according to stage of CKD. Newer therapeutic agents, including calcium-free phosphate binding agents and new vitamin D analogues, effectively suppress serum PTH levels while limiting intestinal calcium absorption and may provide future therapeutic alternatives for children with CKD.

Albright's hereditary osteodystrophy is a rare inherited metabolic disorder characterized by a typical phenotype. It may be associated with or without resistance to parathyroid hormone (pseudohypoparathyroidism). Both forms may co-exist in the same family. Pseudohypoparathyroidism Type 1 and Pseudo-pseudohypoparathyroidism occur as a consequence of reduced erythrocyte membrane coupled with Gs alpha activity. We report here the variable inheritance of hormone resistance in the presence of characteristic phenotype and reduced Gs alpha activity in the same family.

The aim of the present study was to evaluate the presence of pathological alterations attributable to vitamin deficiency in osteological remains from the church of St. Pierre in Puy de St. Pierre, Briancon, France. We recorded alterations referable to scurvy, an acquired osteodystrophy due to vitamin C deficiency, which causes both skeletal and vascular lesions in humans. Scurvy presents a different clinical picture in children and adults: in the latter, in leaves skeletal signs on the palate and teeth. The recording of osteodystrophies attributable to vitamin deficiency allowed us to make general inferences about the nutritional profile of the group under study. The study of this pathology, as well as that of nutritional stresses, can be related to the geographical-environmental conditions of the population to which the sample belongs. This is important from the anthropological point of view, especially in order to examine alimentary habits within the context of the man-environments relationship.

Background Pseudohypoparathyroidism(PHP) is a heterogeneous group of rare metabolic disorders characterized by hypocalcemia and hyperphosphatemia resulting from PTH resistance. Different forms of PHP have been reported based on biochemical and clinical manifestation and genetic findings. Most of these forms are caused by defects in GNAS, an imprinted gene locus with multiple subunits. We reported a 12- year- old girl with unusual clinical manifestations of Pseudopseudohypoparathyroidism(PPHP). Methods After clinical and biochemical evaluations, the patients’ genomic DNA was isolated from peripheral blood leukocytes using salting out method. The whole coding sequences of GNAS gene including 13 exons were amplified by PCR. Quantitative PCR reactions were performed too. Findings We described a 12- year- old girl with Albright Hereditory osteodystrophy (AHO) phenotype, poor school performance, some abnormal movements, TSH resistance with normal serum calcium and phosphorus levels and normal Gsα bioactivity with no mutation in GNAS exons. Unusual neuropsychiatric findings in this patient were compatible with Asperger syndrome. Conclusions According to our findings this patient could not be categorized in any of PHP subgroups. Identifying of such individuals may be useful to discover different genetic patterns in pseudohypoparathyroidism and pseudopseudohypoparathyroidism. It is important to identify patients in whom PHP is caused by novel GNAS mutations, as careful investigations of these findings will likely further our knowledge of this complex and this unique disorder. In addition this case presented with unusual neuropsychiatric findings which has not been reported up to now.

Both aging and chronic renal failure (especially end-stage renal disease) are characterized by a low bone turnover disorder. In aging, the senile form of osteoporosis may be related to a decrease in stem cells differentiating towards osteoprogenitors, while in CRF there is a decrease in the capacity of the osteoblast differentiation program in the absence of the influence of PTH. In both aging and CRF, secondary hyperparathyroidism is common. Thus, the impact of chronic renal failure on skeletal homeostasis in the elderly may be superimposition of an additional factor producing a deficiency of osteoprogenitors. Compensation through higher PTH levels results in an increase in resorptive activity. The long term clinical result of superimposing CRF on senile osteoporosis is unknown due to shortened survival of the population, but the risk of excess bone resorption is realized as survival is increased. From the above pathogenetic discussion of renal osteodystrophy and senile osteoporosis, the need for improved and specific therapeutic approaches is clear. At the present time, our treatments do not adequately consider the superimposition of chronic renal failure and renal osteodystrophy on the aging skeleton that may have osteoporosis.

Bone mineral density (BMD) of the lumber vertebrae and factors related to bone metabolism were determined in patients with chronic viral hepatitis and patients with liver cirrhosis to clarify correlations between hepatic dysfunction, considered to be one of the causes of hepatic osteodystrophy, and decrease in bone mass. BMD of the second to fourth lumbar vertebrae was determined with a Lunar (Madison, WI, USA) DPX, a dual-energy X-ray absorptiometry diagnostic system. BMD was significantly lowest in patients with liver cirrhosis, followed by patients with chronic hepatitis, and healthy subjects, in this order. There was a significantly positive but weak correlation between albumin and BMD. Levels of 25(OH)D and 1,25(OH)2D were significantly lower in patients with liver cirrhosis than in those with chronic hepatitis. BMD and vitamin D were decreased in all patients whose cholinesterase (ChE) was below 0.3 delta pH. Urinary pyridinoline (Upyr) was significantly higher in the patients with liver cirrhosis, in whom bone mass was decreased, than in the patients with chronic hepatitis, whereas serum osteocalcin levels were distributed in the upper normal range in patients with chronic hepatitis and those with liver cirrhosis. There was a positive correlation between 25(OH)D and serum osteocalcin levels in patients with liver cirrhosis. These results indicate that osteogenesis is decreased and suggest that the decrease in BMD which occurs in viral liver cirrhosis, probably related to decreased, bone formation and slight promotion of bone resorption, reflects deranged hepatic function. This is the first report of Upyr and urinary deoxypyridinoline (UDpyr) determination in patients with liver cirrhosis and patients with chronic hepatitis. The negative correlation of Upyr and UDpyr with ChE is a novel finding.

Recent extension of the use of recombinant growth hormone (rhGH) to non-growth hormone-deficient patients necessitates close attention to possible complications in these patients, including effects on bone. Recent studies on the use of rhGH in children with chronic renal failure (CRF) provide some early data. No significant differences in radiographic osteodystrophy scores, serum calcium, phosphorus, or parathyroid hormone (PTH) levels were found between treated and untreated groups. Alkaline phosphatase increased transiently. The effect of renal osteodystrophy on growth response has not yet been reported. Animal models demonstrate that GH stimulates chondrocyte proliferation. Experimental data further suggest that GH can weaken the epiphyseal plate. Slipped capital femoral epiphysis has been reported in GH-deficient patients, before, during, and after GH therapy. In CRF patients treated with GH, slipped capital femoral epiphysis has also been reported. As renal osteodystrophy and hypocalcemia are risk factors for this condition, the relationship to GH therapy is unclear in these patients. Avascular necrosis, known to be associated with slipped capital femoral epiphysis and CRF, has also been reported in patients receiving GH, although the relationship to the therapy is unknown. Children with CRF treated with rhGH should be serially monitored for renal osteodystrophy, slipped capital femoral epiphysis, and avascular necrosis with serial radiographs and serum calcium, phosphorus, alkaline phosphatase, and PTH levels.

Accumulation of aluminum (Al) in the brain and bone has been implicated in the development of encephalopathy and osteodystrophy in patients with renal failure, and it has been reported that citric acid enhances Al absorption and retention. Oral iron supplementation is usually carried out with recombinant human erythropoietin (rHuEPO) therapy in end-stage renal disease (ESRD) patients. Accordingly, there is a possibility that Ferromia (sodium ferrous citrate, tetrasodium biscitrato iron (II), E0708), which is used for the treatment of iron deficiency anemia, might accelerate Al absorption and retention. To investigate this possibility, we administered oral aluminum hydroxide [Al(OH)3] [50mg Al/kg body weight (BW)] with or without E0708 (48mg/kg BW or 480mg/kg BW) to 5/6-nephrectomized rats (n = 27) five times per week for 16 weeks, and determined the Al content of the serum, liver, cerebral cortex, and femoral bone by flameless atomic absorption spectroscopy. The low dose of E0708 corresponded approximately to the clinical dose, and its low and high doses contained 34.5mg/kg BW and 345.0mg/kg BW, respectively, of citric acid. In addition, we gave 5/6-nephrectomized rats Al(OH)3 with citric acid at 35mg/kg BW, which was identical to the citric acid dose of the low-dose regimen of E0708. The weight gain, serum urea nitrogen, and creatinine levels indicated that the rats developed mild to moderate renal failure. There was no significant increase of the Al content in the serum or organs of the Al(OH)3, + E0708-treated rats when compared with the Al(OH)3-treated rats and Al(OH)3 + citric acid-treated rats. These findings suggest that the usual clinical dose of E0708 does not promote Al retention in rats with mild to moderate renal failure or normal rats.

In order to elucidate the pathogenesis of abnormal radiological findings of the bone in patients under hemodialysis, clinical course, blood biochemical data and degrees of bone loss, bone remodeling and bone metabolism were evaluated. Among 198 cases in which bone X-ray pictures were taken, renal osteodystrophy was found in 160 cases (81%). Bone remodeling assessed from X-ray pictures suggested increase of bone mass in 29 cases, decrease of bone mass in 131 cases and stable bone mass in 38 cases. High bone turnover was suggested in 72 cases, low bone turnover in 20 cases and intermediate bone turnover in 106 cases. After more than 50 months of hemodialysis, definite renal osteodystrophy appeared in the X-ray picture. The degrees of abnormalities of serum alkaline phosphatase, C-PTH and BGP were related to the duration of dialysis. Positive correlation was noted between ALP and degree of bone loss, and between C-PTH and BGP and rate of bone turnover. In patients with higher turnover bone with a decrease of bone mass and abnormalities of all these bone parameters, severe renal osteodystrophy with definite imbalance of bone metabolism was suspected.

The deleterious effects of aluminum(AL) and iron(Fe) on bone formation were studied in the presence of nitrilotriacetate (NTA) as a chelator. Both Al-NTA (1.0-1.5 mg Al/kg/day, n = 12)- and ferric nitrilotriacetate (Fe-NTA) (2.0 mg/kg/day, n = 4)-treated Wistar rats showed renal insufficiency blood urea nitrogen [BUN] levels of 25 +/- 8.8-20 +/- 0.7 compared to 12 +/- 0.7-11 +/- 0.4 mg/dl), osteomalacia with a relative osteoid volume of 31.5 +/- 5.6-13.2 +/- 2.4 compared to 4.6 +/- 1.8-0.83 +/- 0.12%, and bone growth retardation (3.1 +/- 0-3.0 +/- 0.2 compared to 3.4 +/- 0-3.3 +/- 0.1 cm) in 24 control rats. Dietary vitamin E(VE) supplementation prevented the Fe-NTA-induced impairment, but not the Al-NTA toxicity. Aluminum was deposited at the interface between osteoid and mineralized bone, while Fe was deposited in the osteoblasts and osteoclasts. There seems to be a positive correlation between hypophosphatemia and osteomalacia but carboxy-terminal parathyroid hormone (C-PTH) and calcium (Ca) levels in the serum were not related to the degree of osteomalacia. Administration of Al-NTA results in more bone Al deposition than that of aluminum chloride (AlCl3) (450 +/- 40 compared to 211 +/- 18 mg/kg fat-free dry weight). The Fe-NTA bone change is related to VE-preventable cellular injury, being consistent with the notion that Fe-NTA toxicity is caused by lipid peroxidation. Al-NTA can be used as an animal model of renal osteodystrophy. Osteodystrophy by Al in chronic renal failure may be mediated by the intrinsic chelator or chelating substance(s) retained in the body fluid due to renal insufficiency.

Cutaneous osteomas occur rarely; they represent the formation of bone in the skin. Primary and secondary forms of ossification can be distinguished. We describe the primary form of ossification in a child with Albright's hereditary osteodystrophy.

Celiac disease (CD) is an immunomediated reaction to the ingestion of gluten, characterized by mucosal alterations of the duodenum and small bowel. The disease may also disturb calcium and phosphate metabolisms leading to alterations of bone remodeling. Osteomalacia was formerly considered the main complication; more recent studies show that osteopenia and osteoporosis are far more frequent. Bone mineral density (BMD) is low in about 40% of patients with overt or paucisymptomatic forms of the disease. In a recent paper, Bianchi and Bardella [1] reviewed the different, although nonexclusive, pathogenic mechanisms that have been proposed (1) calcium and vitamin D malabsorption leads to secondary hyperparathyroidism and increased bone turnover; (2) enhanced production of inflammatory cytokines stimulates osteoclastogenesis; (3) low insulin-like growth factor levels (IGF-1) secondary to zinc deficiency might play a role [1]. We recently observed a 62 year-old female patient with celiac disease diagnosed 4 years earlier. She was given a gluten-free diet, corticosteroids (1 mg/kg/D), calcium and vitamin D supplementation and iron injections. However, she still presented bowel disturbances and abdominal pain and occasionally received Smecta and Gelox , both compounds containing aluminum salts, either in form of silicate or hydroxide. She was referred to the rheumatologic unit because of bone pain; BMD measurements were reduced (T-scores lumbar = )6.18; total femur = )5.9). In serum, calcium (after correction for albumin) and phosphate were normal. Serum creatinine, bone alkaline phosphatase and osteocalcine levels were in the normal range as well as intact parathyroid hormone and 25-hydroxy vitamin D. The diagnosis of celiac disease was confirmed by fibroscopy, histology and immunological tests (antigliadine and anti-gluten antibodies). A transiliac bone biopsy was performed and studied by X-ray microtomography and processed undecalcified for histomorphometry. Tetracycline labeling could not be done in this patient because of digestive intolerance. Trabecular bone volume was reduced with mild micro-architectural alterations of the trabecular network (reduced trabecular thickness and number associated with an increased trabecular separation) (Fig. 1A) (Table 1). Osteoid volume and surfaces were slightly increased but osteoid thickness was normal, thus eliminating the diagnosis of osteomalacia. The number of osteoclasts (identified by a histoenzymatic method) was low and confirmed the absence of hyperparathyroidism. Because the histomorphometric profile was in favor of adynamic bone disease, as observed in hemodialyzed patients with renal insufficiency and aluminum intoxication [2], histochemical identification of Al by the mordant blue technique was done on additional sections. The Al staining identified strongly positive bands in the bone matrix and confirmed Al intoxication (Fig. 1B). Histomorphometric evaluation of bone in celiac disease has recently confirmed that osteoporosis is now more common than osteomalacia [3]. The possibility of Al intoxication from cumulative ingestion of aluminum-containing drugs was shown even in nondialyzed renal failure patients [2]. It is likely that Al Correspondence to: D. Chappard; E-mail: danielChappard@ univ-angers.fr Table 1. Histomorphometric parameters

Aluminum-induced bone disease in uremic patients receiving dialysis was first described a little more than 10 years ago. The epidemic form of the disease was seen in centers where there was a high aluminum content in the water dialysate. Although this problem has been corrected, sporadic forms of the disease continue to be noted in dialyzed and nondialyzed patients. Multiple fractures are a radiological feature of aluminum-related bone disease. Fractures of the ribs and hips and vertebral crush fractures are the usual manifestations. We present four patients whose nontraumatic fractures involved large bones, without evidence of multiple fractures. In two of the patients symptoms were vague and subacute; a third patient with a subcapital fracture was ambulatory. Only in one patient (fractured dens) were symptoms acute enough to warrant immediate radiography. One of the patients had no symptoms pertaining to a fracture of C5 with retrolisthesis. Rib fractures are common in this condition but were seen in only one patient, in whom they were detected 8 years previously. Healing was not seen in any of the fractures. In patients receiving dialysis the presence of spontaneous fractures of large bones or cervical vertebrae, which may be clinically silent or vaguely symptomatic, should raise the possibility of aluminum-induced osteomalacia even if these fractures are solitary.

Pseudohypoparathyroidism (PsHP) is a rare disorder that might be caused by a defect in the stimulatory G-proteine (Gs), which transduce the PTH receptor signal to adenylate cyclase. We investigate 35 patients (29 children and 6 adults) with PsHP syndrome. Clinical features, Ellsworth-Howard test, serum level of intact PTH (PTHi) and Gs biological activity are studied. Gs activity is measured with a technic adapted from that of LEVINE we optimized to applicate in children (Assay variation : 10 %). 24 patients (68 %) have a PsHP type Ia with a decrease of Gs-unit activity, but we don't find any relation between Albright's osteodystrophy (AHO) and Gs-unit defect : 4 children are AHO - and 20 are AHO +, and 10 of them presented an associate hypothyroidism. 2 patients (6 %) have no response to infusion of exogenous PTH with an increased of Gs-unit activity and could be PsHP type Ib. Only one patient is PsHP type II with normal Gs-unit, serum PTHi level are increased in all patients (mean = 218 pg/ml, range 65 - 571) without difference between PsHP groups, or relation with Gs-unit activity. Other patients would be classified in pseudo-PsHP with decrease Gs - biological activity. In other hand, we studied 10 families, in 9 Gs-unit activity defect is found at least in 1 member (7 times mother, 1 both mother and father, 1 father). In conclusion, Gs-unit activity appears to be of interest in the investigation of PsHP syndrome. Supported by INSERM.

Pseudohypoparathyroidism (PsHP) is a rare disorder that might be caused by a defect in the stimulatory G-proteine (Gs), which transduce the PTH receptor signal to adenylate cyclase. We investigate 35 patients (29 children and 6 adults) with PsHP syndrome. Clinical features, Ellsworth-Howard test, serum level of intact PTH (PTHi) and Gs biological activity are studied. Gs activity is measured with a technic adapted from that of LEVINE we optimized to applicate in children (Assay variation : 10 %). 24 patients (68 %) have a PsHP type Ia with a decrease of Gs-unit activity, but we don't find any relation between Albright's osteodystrophy (AHO) and Gs-unit defect : 4 children are AHO - and 20 are AHO +, and 10 of them presented an associate hypothyroidism. 2 patients (6 %) have no response to infusion of exogenous PTH with an increased of Gs-unit activity and could be PsHP type Ib. Only one patient is PsHP type II with normal Gs-unit, serum PTHi level are increased in all patients (mean = 218 pg/ml, range 65 - 571) without difference between PsHP groups, or relation with Gs-unit activity. Other patients would be classified in pseudo-PsHP with decrease Gs - biological activity. In other hand, we studied 10 families, in 9 Gs-unit activity defect is found at least in 1 member (7 times mother, 1 both mother and father, 1 father). In conclusion, Gs-unit activity appears to be of interest in the investigation of PsHP syndrome.

In 34 patients with chronic renal failure (CRF), fractional 47calcium absorption (Fa47Ca) was measured by an external counting method. A significant correlation was found with impairment of renal function, as expressed by the creatinine clearance. There was also a significant correlation of Fa47Ca with the serum phosphate (SeP) level and of immunoreactive parathyroid hormone (iPTH) with renal function. When the relationship of both SeP and Fa47Ca with creatinine clearance was excluded, no partial correlation between SeP and Fa47Ca appeared to exist. A significant increase of Fa47Ca and serum Ca and a significant decrease of SeP and iPTH were found in 12 patients 2 to 15 months after they were put on intermittent hemodialysis. The possible influence of SeP on intestinal calcium absorption is discussed, and it is suggested that impairment of intestinal absorption of calcium is not a main factor in development of renal osteodystrophy.

Recent short-term studies have shown that microgram doses of both 1,25-dihydroxycholecalciferol (1,25-(OH)2-D3), the hormonally active metabolite of vitamin D, and lα-hydroxycholecalciferol (lα-OH-D3), a synthetic analogue can increase intestinal absorption of calcium in patients with chronic renal failure in whom large (mg) doses of vitamin D are ineffective (1, 4, 5, 6). In patients with renal osteodystrophy, these compounds may reduce plasma parathyroid hormone concentration and osteoclastic bone resorption (2) and increase the calcium content of the bones of the hands (3). There is, however, little published work on the long-term effects of 1,25-(OH)2-D3 or lα-OH-D3 in patients with renal osteodystrophy. The present paper describes the effects of lα-OH-D3 in four children and three adults studied for up to 14 months.

Renal osteodystrophy, a frequent complication of chronic renal failure, is usually assessed by periodic X-rays of bone which are both poorly reproducible and expensive. Seeking a better screening test for osteodystrophy, we evaluated the usefulness of serum alkaline phosphatase as a predictor of bone disease and of hyperparathyroidism. Alkaline phosphatase, despite nonspecificity, correlates with the severity of osteodystrophy and with the increase in serum parathyroid hormone concentration. Serial measurements of alkaline phosphatase can predict changes in these parameters.

Lizards, especially iguanids and varanids, frequently develop nutritional osteodystrophy in captivity, but its pathogenesis is incompletely understood. Green iguanas fed an experimental diet low in calcium (0.2%) and adequate in phosphorus (1.1%) developed severe osteoporosis characterized by flattened inactive osteoblasts, marked resorption of endosteal bone by large multinucleated osteoclasts, and pronounced resorption of cortical bone by osteocytic osteolysis. Iguanas fed an experimental diet low in both calcium (0.1%) and phosphorus (0.2%) developed osteoporosis with osteomalacia characterized by large active osteoblasts overlying wide osteoid seams, marked osteoclastic resorption of endosteal bone, and large osteocytic lacunae which had a prominent layer of osteoid. Osteocytes in iguanas fed the low calcium diets were small in relation to the size of their lacuanae and contained abundant microtubules, microfilaments and mitochondria but a paucity of rough endoplasmic reticulum. Mean ash content of tibias from iguanas fed the low calcium diets was lower, particularly in iguanas that developed severe osteomalacia, than in iguanas fed the control diet (2.7% calcium, 1.1% phosphorus). The ultrastructural evidence suggesting active bone formation, osteoclastic resorption, and osteocytic osteolysis seen in control iguanas was consistent with that of a young growing animal. The results of this investigation demonstrated that experimental iguanas fed diets low in calcium developed hypocalcemia and compensatory hyperparathyroidism resulting in progressive osteoporosis due to osteoclastic and osteocytic osteolysis.

Four Indonesian goats fed Leucaena leucocephala with a calcium to phosphorus ratio in excess of 6:1 for 472 days developed mandibular osteodystrophy fibrosa to varying degrees ranging from severe to slight. The animals appeared to grow normally but the animal with the most severe clinical symptoms lost weight for 35 days prior to the termination of the experiment. The other three animals either maintained or gained weight during this period. A balance study performed part way through the experiment revealed that the animal which subsequently lost weight was probably not storing calcium or phosphorus whereas the other animals had a positive calcium balance and were probably storing small amounts of phosphorus. Histological examination of tissues taken after a post-mortem revealed that the kidney, parathyroid and thyroid glands and long bones were normal.

The mean depth of bone eroded in unit time at resorption centers was measured in tetracycline-labeled bone biopsies of 16 adult patients on periodic renal dialysis, of one adolescent boy with renal rickets and secondary hyperparathyroidism, and of two adult women with proven primary hyperparathyroidism. This index of cellular-level resorption was subnormal on haversian bone surfaces in all groups, and it was subnormal on cortical-endosteal bone surfaces in the dialysis group; there was insufficient material to evaluate the index on this latter surface in the other two groups. The results suggest that individual osteoclasts resorb bone more slowly than normal in naturally occurring human hyperparathyroid states of long standing.

Multiple localised bone densities were radiographically spotted in a 68-year-old male patient who had worked for 5 years in uranium mines (Joachimsthal); they were diagnosed as metastases of a prostate carcinoma. After the autopsy we found by histological, radiochemical and autoradiographic investigations that a metastasizing prostatic carcinoma had not existed, but rather a “paget-like” osteodystrophia caused by deposits of radioactive decay products of inhaled Rn-222. Decay products are also likely to deposit in calcified atheroslerotic plaques.

In 30 patients with renal insufficiency, a biopsy specimen was taken from the iliac crest and processed to obtain non-decalcified sections for morphometric evaluation. The bone volume was normal. There was an increased amount of osteoid tissue, increased bone resorption and an abnormal amount of fibrous tissue. With the aid of correlation calculations and factor analysis, four factors were extracted which expressed the influence of parathyroid hormone on bone tissue, the degree of mineralization and the relation between bone volume and bone surface, the relation between bone tissue and measured space, and non-active bone resorption.

We describe a patient with pseudopseudohypoparathyroidism who had an osseous tubercle on the anterolateral margin of the foramen magnum causing compression of the spinal cord. This patient had no evidence for any endocrinopathies and had no other spinal canal anomalies. We suggest that the morphologic phenotype found in patients with pseudopseudohypoparathyroidism, also known as Albright's hereditary osteodystrophy, has an associated risk for spinal cord compression due to congenital vertebral anomalies. The poor recovery of neurologic function following spinal decompression mandates prompt recognition and therapy of this condition in patients with Albright's hereditary osteodystrophy.

The case of a 41-year-old woman with cerebral calcification of a rather unusual extent is reported. This condition was associated with mental deficiency, pseudohypoparathyroidism and Albright's hereditary osteodystrophy. Four years later hypothyroidism was diagnosed. Visual impairment and electroretinogram abnormality suggested a retinopathy involving mostly rods. Despite their rarity, pseudohypoparathyroidism and Albright's hereditary osteodystrophy are of major interest, since they represent the only human disease states in which G protein function has been found to be disrupted. The overall clinical picture was strongly suggestive of a genetic deficiency of a guanine nucleotide-binding protein, termed Gs. The putative involvement of another G protein, contained in rods and cones, transducin, in the pathogenesis of the retinopathy is discussed.

INTESTINAL malabsorption of calcium occurs regularly in patients with advanced renal failure and is commonly associated with rickets or osteomalacia, which closely resemble the osteodystrophy of vitamin D deficiency1. Large amounts of vitamin D are required to correct this defect in calcium absorption and to promote healing of the bone lesions but the nature of the relative insensitivity to the biological effects of the vitamin is uncertain1,2. The suggestion3 that vitamin D resistance in uraemia is due to an effective deficiency of 25-hydroxycholecalciferol has been refuted2,4. The demonstration of the role of the kidney in producing a second biologically potent metabolite, 1,25-dihydroxycholecalciferol5,6, makes it likely that the abnormalities in uraemic patients are due to loss of renal tissue (see preceding communication7).

Captive lizards fed a variety of vegetarian and carnivorous diets frequently develop severe nutritional osteodystrophy. Five hatchling iguanas which were captive for 5 months and fed a diet low in calcium and phosphorus developed clinical signs and lesions typical of nutritional osteodystrophy in captive lizards. They had tetany with severe osteoporosis, pathologic fractures, and cartilaginous diaphyseal enlargements of long bones which either were associated with fractures or with intact bones. Hatchling and juvenile iguanas fed a similar diet low in calcium (0.1%) and phosphorus (0.2%) under experimental conditions developed hypocalcemia, tetany, osteoporosis with but adequate in phosphorus (1.1%) developed progressive hypocalcemia and severe osteopososis with pathologic fractures. Control iguanas fed a diet with adequate calcium (2.7%) and phosphours (1.1%) had well mineralized bones with wide cortices and thick metaphyseal trabeculae. Iguanas fed low calcium experimental diets whether low or adequate in phosphorus developed hypocalcemia with compensatory secondary hyperparathyroidism resulting in severe osteodystrophy similar to that reported in captive lizards.