Severe Osteomalacia Research Articles

A case report of severe osteomalacia in a young adult female - in search of a FGF23 secreting tumor

A case report of severe osteomalacia in a young adult female - in search of a FGF23 secreting tumor

Approaching virtual osteoid volume estimation and in-depth tissue characterization in patients with tumor-induced osteomalacia.

Tumor-induced osteomalacia (TIO) poses a significant diagnostic challenge, leading to increased disease duration and patient burden also by missing clinical suspicion. Today, diagnosis of osteomalacia relies on invasive iliac crest biopsy, if needed. Therefore, a noninvasive method would be beneficial for patients with severe osteomalacia, such as TIO, to inform their clinical management and address specific needs, like estimating the regeneration capacity at high osteoid volumes (OVs) or the potential of a hungry bone syndrome after tumor removal. Furthermore, given the lack of comprehensive histological characterization of TIO, there is a need for additional tissue characterization. Therefore, our assessment encompassed iliac crest biopsies that were examined using quantitative electron backscattered microscopy, Raman spectroscopy, micro-computed tomography, and histology to analyze the biopsy tissue. Our clinical assessment encompassed DXA and high-resolution peripheral quantitative computed tomography (HR-pQCT) alongside with biochemical analyses and clinical evaluations. Combining imaging and clinical data, we established a model to predict the OV. We compared 9 TIO patients with 10 osteoporosis (OPO) patients and 10 healthy controls. Histological analyses confirmed a pronounced OV in TIO patients (OPO: 1.20% ± 1.23% vs TIO: 23.55% ± 12.23%, P < .0005), and spectroscopy revealed lower phosphate levels in TIO biopsies. By combining HR-pQCT and laboratory diagnostics, we developed a linear regression model to noninvasively predict the OV revealing significantly higher modeled OV/BVmodel values of 24.46% ± 14.22% for TIO compared to the control group (5.952% ± 3.44%, P ≤ .001). By combining laboratory diagnostics, namely, ALP and Tt.BMDRadius measured by HR-pQCT, we achieved the calculation of the virtual osteoid volume to bone volume ratio (OV/BVmodel) with a significant correlation to histology as well as reliable identification of TIO patients compared to OPO and control. This novel approach is potentially helpful for predicting OV by noninvasive techniques in diagnostic procedures and improving the clinical management of TIO.

Combination of osteogenesis imperfecta and hypophosphatasia in three children with multiple fractures, low bone mass and severe osteomalacia, a challenge for therapeutic management

Osteogenesis imperfecta (OI) and hypophosphatasia (HPP) are rare skeletal disorders caused by mutations in the genes encoding collagen type I (COL1A, COL1A2) and tissue-non-specific isoenzyme of alkaline phosphatase (ALPL), respectively. Both conditions result in skeletal deformities and bone fragility although bone tissue abnormalities differ considerably. Children with OI have low bone mass and hypermineralized matrix, whereas HPP children develop rickets and osteomalacia.We report a family, father and three children, affected with growth retardation, low bone mass and recurrent fractures. None of them had rickets, blue sclera or dentinogenesis imperfecta. ALP serum levels were low and genetics revealed in the four probands heterozygous pathogenic mutations in COL1A2 c.838G > A (p.Gly280Ser) and in ALPL c.1333T > C (p.Ser445Pro). After multidisciplinary meeting, a diagnostic transiliac bone biopsy was indicated for each sibling for therapeutic decision.Bone histology and histomorphometry, as compared to reference values of children with OI type I as well as, to a control pediatric patient harboring the same COL1A2 mutation, revealed similarly decreased trabecular bone volume, increased osteocyte lacunae, but additionally severe osteomalacia. Quantitative backscattered electron imaging demonstrated that bone matrix mineralization was not as decreased as expected for osteomalacia.In summary, we observed within each biopsy samples classical features of OI and classical features of HPP. The apparent nearly normal bone mineralization density distribution results presumably from divergent effects of OI and HPP on matrix mineralization. A combination therapy was initiated with ALP enzyme-replacement and one month later with bisphosphonates. The ongoing treatment led to improved skeletal growth, increased BMD and markedly reduced fracture incidence.

High-Dose Intravenous Iron with Either Ferric Carboxymaltose or Ferric Derisomaltose: A Benefit-Risk Assessment.

The intravenous iron formulations ferric carboxymaltose (FCM) and ferric derisomaltose (FDI) offer the possibility of administering a large amount of iron in one infusion. This results in faster correction of anemia and the formulations being better tolerated than oral iron formulations. This triad of logistic advantages, improved patient convenience, and fast correction of anemia explains the fact that intravenous iron formulations nowadays are frequently prescribed worldwide in the treatment of iron deficiency anemia. However, these formulations may result in hypophosphatemia by inducing a strong increase in active fibroblast growth factor-23 (FGF-23), a hormone that stimulates renal phosphate excretion. This effect is much more pronounced with FCM than with FDI, and therefore the risk of developing hypophosphatemia is remarkably higher with FCM than with FDI. Repeated use of FCM may result in severe osteomalacia, which is characterized by bone pain, Looser zones (pseudofractures), and low-trauma fractures. Intravenous iron preparations are also associated with other adverse effects, of which hypersensitivity reactions are the most important and are usually the result of a non-allergic complement activation on nanoparticles of free labile iron—Complement Activation-Related Pseudo-Allergy (CARPA). The risk on these hypersensitivity reactions can be reduced by choosing a slow infusion rate. Severe hypersensitivity reactions were reported in < 1% of prospective trials and the incidence seems comparable between the two formulations. A practical guideline has been developed based on baseline serum phosphate concentrations and predisposing risk factors, derived from published cases and risk factor analyses from trials, in order to establish the safe use of these formulations.

Osteomalacia as a result of phosphorus deficiency in beef cattle grazing subtropical native pastures in Uruguay.

We investigated 2 outbreaks of osteomalacia as a result of phosphorus (P) deficiency in herds of lactating beef cows grazing subtropical native pastures in Uruguay. Cows exhibited pica, difficulty to stand and walk, rib fractures, and body weight loss even with adequate forage availability. Osteopenia and severe osteomalacia were observed on gross and histologic examination. The concentrations of bicarbonate-extractable P in soil (4.0, 4.1 mg P/kg), total P in pasture (0.9, 1.1 g P/kg), inorganic P in serum (1.0, 0.71 mmol P/L), and P in bone (73 mg P/mL) were all low. Although injectable and mineral salt supplements provided additional P in both outbreaks, these supplementary amounts were insufficient to prevent P deficiency. The P ingested by the cows from the pasture and supplements would have provided 20-55% of their daily P requirements of ~21 g P/d. Osteomalacia occurred in cattle at the 2 ranches as a result of severe P deficiency in the soil and forage, and inadequate P supplementation. Following diagnosis, control of P deficiency in beef cattle requires estimation of the amount of pasture P ingested and provision of sufficient additional supplementary P to meet the animals' requirements.

Severe Osteomalacia and Fractures Secondary to Vitamin D Deficiency

Background: Vitamin D deficiency is a common entity among the elderly. Low vitamin D levels can lead to poor bone mineralization, in addition to elevations in PTH levels with resultant increases in bone turnover. However, severe Vitamin D deficiency causing osteomalacia has become uncommon in the United States due to increased screening and treatment. Vitamin D supplementation is a mainstay of therapy for osteoporosis, yet its effect on bone density is generally thought to be modest. We present here an extreme case of vitamin D deficiency leading to severe secondary hyperparathyroidism and bone demineralization, with excellent response to supplementation. Clinical Case: Patient was a 73-year-old woman with hypertension who presented to the ER with acute on chronic back and lower extremity pain. She had these pains for about a year, but they had worsened over the last 4 days. She had been homebound for the past 1–2 years due to severe pain while ambulating, reported a five-inch loss of height and 50 pounds weight loss, and maintained a vegan diet. She had not had medical care in 15 years. Imaging studies demonstrated a displaced left femoral neck fracture, a nondisplaced right femoral neck fracture, multilevel thoracolumbar compression fractures, and a nondisplaced right scapular fracture. Blood tests revealed normal renal function, calcium 8.6mg/dL (nl 8.5–10.5), phosphorus 2.6mg/dL (nl 2.5–4.5), and alkaline phosphatase 2,821U/L (nl 45–164). Secondary osteoporosis workup was negative for hypercalciuria or multiple myeloma, but was notable for a PTH level of 2,190 pg/mL (nl 10–65) and 25-OH Vitamin D level of <5ng/mL (nl >30). C-telopeptide was measured at 3,346 pg/mL (nl <1000) and osteocalcin >300ng/mL (nl 8–32). DEXA scan showed T-scores of -4.2 at the lumbar spine and -6.8 at the distal forearm. She was started on high-dose vitamin D supplementation, with serum Vitamin D level rising to 42.1ng/mL after 6 months of treatment. This corresponded to a decrease in PTH to 141.1pg/mL and alkaline phosphatase to 375U/L. Repeat DEXA two years later showed 52.8% increase in bone mineral density at the lumbar spine, and 27.1% increase at the forearm. The patient’s body pains have significantly improved and she is now ambulatory again. Conclusions: Vitamin D deficiency is an uncommon cause of severe bone demineralization in the United States. However, in certain high-risk populations, it can present with debilitating osteomalacia and numerous pathologic fractures. Even in cases of osteoporosis with severe PTH elevation, Vitamin D deficiency must be ruled out as a potential secondary etiology, as it can be easily treated with potentially dramatic response.

Response of Severe Osteomalacia to High Dose Vitamin D3 Replacement in a Patient With Ulcerative Colitis and Liver Transplantation on Immunosuppressive Therapy

Background: Bone disease is common in inflammatory bowel disease (IBD), more frequently in Crohn’s disease than ulcerative colitis (UC). We present the case of a patient with prior history of ulcerative colitis with severe 25 OH vitamin D deficiency and metabolic bone disease. Case: 67 year old male with h/o ulcerative colitis, colon cancer s/p proctocolectomy and ileostomy, chemo-radiation, h/o primary sclerosing cholangitis (PSC) and orthotopic liver transplantation (OLT) 20 years prior presented with presented with severe muscle aches, severe limitation in mobility and severe vitamin D deficiency. He had been on chronic prednisone and tacrolimus, mycophenolate. Three years after OLT, he had fragility fractures at different times in both hips requiring hip arthroplasty. Labs were significant for persistently elevated alkaline phosphatase (ALP) up to 1569 U/L for last 10 years, bone specific ALP at 423.6 mcg/L, Calcium 9 mg/dl, phosphorus 2 mg/dl, 25 OH vitamin D was 4 ng/ml, 1, 25-hydroxy vitamin D (25-OHD) was 34 ng/ml, PTH was 189 pg/ml, urine calcium/creatinine ratio was 50 mg/g and urine NTX at 223 nM BCE/mM. Celiac screen was negative and tacrolimus levels were within normal range. Patient had extensive workup by gastroenterology for elevated ALP including three liver biopsies which were unrevealing. A bone scan showed increased uptake in thoracic region and metaphyses of large joints. A diagnosis of osteomalacia and secondary hyperparathyroidism was made and he was started on high dose vitamin D gradually increased to 8000 units thrice a day. Within few weeks, he noted marked improvement in mobility, bone pain and need for pain medications. In few months, BSAP decreased to 144.9 mcg/l, NTX and PTH also improved. 25 OH has also increased slightly to 13. He continues on high dose vitamin D and 1200mg of calcium daily. Discussion: Our patient likely had severe osteomalacia due to prolonged vitamin D deficiency, caused by multiple etiologies. Firstly, poor absorption in UC might lower 25-OHD levels. Secondly CYP3A enzymes are involved in the metabolism of calcineurin inhibitor tacrolimus as well as vitamin D, this could result in enhanced vitamin D metabolism, which would explain persistently low vitamin D level despite replacement with such high doses. The significant improvement in his symptoms with supplementation resulting in increased mobility despite not having a normal vitamin D level suggest other pleiotropic effects of vitamin D on muscle and bone as well. Additionally effects of liver transplantation on vitamin D metabolism need to be explored further.

Alterations of bone material properties in adult patients with X-linked hypophosphatemia (XLH)

X-linked hypophosphatemia (XLH) caused by PHEX mutations results in elevated serum FGF23 levels, renal phosphate wasting and low 1,25-dihydroxyvitamin D. The glycophosphoprotein osteopontin, a potent inhibitor of mineralization normally degraded by PHEX, accumulates within the bone matrix. Conventional therapy consisting of supplementation with phosphate and vitamin D analogs is burdensome and the effects on bone material poorly characterized.We analyzed transiliac bone biopsies from four adult patients, two of them severely affected due to no diagnosis and no treatment until adulthood. We used light microscopy, qBEI and FTIRI to study histology, histomorphometry, bone mineralization density distribution, properties of the organic matrix and size of hypomineralized periosteocytic lesions.Non-treatment resulted in severe osteomalacia, twice the amount of mineralized trabecular volume, multiple osteon-like perforations, continuity of lamellae from mineralized to unmineralized areas and distinctive patches of woven bone. Periosteocytic lesions were larger than in treated patients. The latter had nearly normal osteoid thicknesses, although surface was still elevated.The median calcium content of the matrix was always within normal range, although the percentage of lowly mineralized bone areas was highly increased in non-treated patients, resulting in a marked heterogeneity in mineralization.Divalent collagen cross-links were evident independently of the mineral content of the matrix. Broad osteoid seams lacked measurable pyridinoline, a mature trivalent cross-link and exhibited considerable acidic lipid content, typically found in matrix vesicles.Based on our results, we propose a model that possibly integrates the relationship between the observed mineralization disturbances, FGF23 secretion and the known osteopontin accumulation in XLH.

SAT-403 Is Most “Primary” Hyperparathyroidism Both Tertiary and Preventable?

Primary Hyperparathyroidism has reached epidemic proportions since the advent of mass screening for laboratory parameters including calcium. Secondary Hyperparathyroidism has been considered by some individuals as “Normocalcemic Primary Hyperparathyroidism” (4th International Workshop on The Management of Asymptomatic Primary Hyperparathyroidism, Florence, 2013 Bilzekian et al:-”Normocalcemic PHPT is a clinical presentation of PHPT: management approach is recommended.”)We report a single case of severe secondary hyperparathyroidism (with severe osteomalacia due to ileal resection) as well as 56 subsequent secondary hyperpararthyroid cases treated with 1,25dihydroxy-D3 (calcitriol) which were associated with significant reduction of parathormone levels *and continued normalization of calcium levels* [as well as significant improvement in bone density.] We are instituting a long-term, double-blind, placebo controlled clinical trial - with design presented here - to determine whether or not the incidence of hypercalcemic hyperparathyroidism can be significantly reduced or even obliterated by treatment with calcitriol.Mrs. K.E.Date Ca++ PTH Calcitriol---------- - ------ ----- ---------1997/05/01 8.5 344.0 0.25 i po qd1997/05/28 8.5 388.0 0.25 i po qd1997/07/21 9.3 102.0 0.50 ii po tid1997/08/21 9.3 167.0 0.50 ii po qid1997/11/14 10.4 11.4 0.50 ii po qid1998/01/26 11.2 0 (!) 0.50 i po tid1998/04/28 9.7 8.6 0.50 i po tid1998/06/26 9.5 11.4 0.50 i po tid1999/04/28 9.4 15.2 0.50 i po tid2000/02/04 8.7 16.0 0.50 i po tid2000/05/01 9.3 15.1 0.50 i po tid Baseline Values Statistic: Ca++ /PTH, Total: 910.70 /4170.00, Average: 9.49/73.16, Count: 57/57, Maximum: 11.70/211.00, Minimum: 4.90 /12.00, Variance: 1.38 /923.70, SD: 2.47/59.34 Post-Treatment with Calcitriol Statistic: Ca++ PTH, Total: 910.70/4170.00, Average: 9.49/73.16,Count: 57/57, 11.70/211.00, Minimum: 4.90/12.00, Variance: 1.38 /923.70, SD: 1.18/43.8699% confidence interval around the 49.9 pg/ml difference was (-75.5 to -24.3 pg/ml)Proposed Clinical Trial:- Calcitriol to Prevent Hyperparathyroidism (CaPH) TrialDouble-blind, randomized, parallel-controlled clinical trial stratified by history of nephrolithiasis with follow-up for 5-year durationCalcitriol Rx to keep PTH< 70 vs Ergocalcitriol to keep 25-OH D3 >30N=100 patients/armVisits q90 daysBone densitometry [including lateral spine] qyearTelopeptides, Crosslinks, Alkaline Phosphatase, UV/Pcalcium/creatinine,Flat PlatesExclusion: Pcreatinine>2.0,mg/dl, Ca++>10.0 mg/dl,Familial HPTHInclusion: PTH >70 pg/mlPrimary Efficacy Variable: Number of documented cases of Hypercalcemic HyperparathyroidismSecondary Variables: Mortality, Kidney stones, Bone density, Fractures

Artificial intelligence system can achieve comparable results to experts for bone age assessment of Chinese children with abnormal growth and development.

ObjectiveBone age (BA) is a crucial indicator for revealing the growth and development of children. This study tested the performance of a fully automated artificial intelligence (AI) system for BA assessment of Chinese children with abnormal growth and development.Materials and MethodsA fully automated AI system based on the Greulich and Pyle (GP) method was developed for Chinese children by using 8,000 BA radiographs from five medical centers nationwide in China. Then, a total of 745 cases (360 boys and 385 girls) with abnormal growth and development from another tertiary medical center of north China were consecutively collected between January and October 2018 to test the system. The reference standard was defined as the result interpreted by two experienced reviewers (a radiologist with 10 years and an endocrinologist with 15 years of experience in BA reading) through consensus using the GP atlas. BA accuracy within 1 year, root mean square error (RMSE), mean absolute difference (MAD), and 95% limits of agreement according to the Bland-Altman plot were statistically calculated.ResultsFor Chinese pediatric patients with abnormal growth and development, the accuracy of this new automated AI system within 1 year was 84.60% as compared to the reference standard, with the highest percentage of 89.45% in the 12- to 18-year group. The RMSE, MAD, and 95% limits of agreement of the AI system were 0.76 years, 0.58 years, and −1.547 to 1.428, respectively, according to the Bland-Altman plot. The largest difference between the AI and experts’ BA result was noted for patients of short stature with bone deformities, severe osteomalacia, or different rates of maturation of the carpals and phalanges.ConclusionsThe developed automated AI system could achieve comparable BA results to experienced reviewers for Chinese children with abnormal growth and development.

Surgical Indications in Hypophosphataemic Rickets.

Low levels of phosphate in blood secondary to a lack of phosphorous reabsorption in the renal tubule cause hypophosphataemic rickets. To increase blood calcium levels, bone calcium is released into the bloodstream by increasing the activity of osteoclasts in the bones. These alterations in bone metabolism lead to delayed growth and small height, diffuse bone pain, bone fragility with microfractures, and frequent fractures and bone deformities. Although management of some of these conditions is mainly conservative, in cases of bone deformities or severe osteomalacia surgery should be considered: from minimally invasive surgical techniques of guided growth in patients with less deformity and open physeal cartilage to correction osteotomies in three-dimensional deformities. This article briefly reviews the indications for surgery procedures to be performed in these patients, highlighting when to use aggressive and non-aggressive approaches.

Phosphaturic mesenchymal tumor

Phosphaturic mesenchymal tumors (PMTs) are very unusual tumors, commonly associated with tumor induced osteomalacia (TIO). The tumor cells produce a peptide hormone-like substance known as fibroblast growth factor 23 (FGF23), which regulates phosphate levels. When FGF23 is over expressed by the tumor cells it leads to phosphaturia, which inturn causes mobilization of calcium and phosphate from bones, and decreased osteoblastic activity, which finally leads to severe osteomalacia. Usual presentation of PMT will be gradual muscular weakness and diffuse bone pain from pathologic fractures. The majority of PMTs are benign, malignant PMTs are extremely rare, but exist. However, very rarely PMT present without phosphaturia and TIO i.e., the nonphosphaturic variant. The challenge in diagnosis of PMT is due to the vague nature of the symptoms and lack of clinical suspicion. The diagnosis is often missed due to the rarity of PMTs. The usual location for PMT involves the extremities followed by head and neck sites. We report a case of a 37 year old male who presented to the outpatient department with a swelling in the left parotid region. He had no associated symptoms. CT scan showed a well-defined heterogeneous mass measuring 2.3 × 2.0 cm with calcification and soft tissue density seen superficially in the left pre auricular region. Per operatively the tumor was found to be intramuscular, embedded in the left masseter muscle. The final histopathology report was confirmative of phosphaturic mesenchymal tumor.

Successful treatment of tumor-induced osteomalacia causing by phosphaturic mesenchymal tumor of the foot.

Tumor-induced osteomalacia causing by phosphaturic mesenchymal tumor of the foot is exceedingly rare, thus may bring great challenges to the timely and proper diagnosis and treatment of clinicians. The only definitive management is removal of the phosphaturic mesenchymal tumor completely. The objective of this article is to report 2 unusual cases with tumor-induced osteomalacia causing by phosphaturic mesenchymal tumor of the foot.We describe 2 patients with phosphaturic mesenchymal tumor involving the foot who were successfully treated with tumor resection. On presentation to our institution, the patients both had signs of severe osteomalacia, and the patients’ most outstanding complaints were diffuse bone pain, general weakness, and disabled walking. A 53-year-old female underwent surgical excision of pathogenic tumor on the sole of left foot. A 62-year-old female underwent complete excision of pathogenic tumor of right plantar. The patients showed appropriate destruction of the tumor, adequate pain relief, and the elevated blood phosphorus levels compared with the previous status.Surgical resection is the most effective treatment option for patients with tumor-induced osteomalacia who can undergo appropriate surgical treatment. This represents a safe and reasonable approach to sustainably relieve pain and other symptoms with tumor-induced osteomalacia in the foot.

Suppressive effects of tenofovir disoproxil fumarate, an antiretroviral prodrug, on mineralization and type II and type III sodium-dependent phosphate transporters expression in primary human osteoblasts.

Tenofovir disoproxil fumarate (TDF) is an antiretroviral drug commonly used for the management of Human Immunodeficiency Virus (HIV) in highly active antiretroviral therapy (HAART) and of chronic Hepatitis B Virus (HBV) infections. Long-term TDF-treated subjects present decrease of bone mineral density and rarely severe osteomalacia. Although these adverse effects have been attributed to the impaired proximal tubule function, a possible direct involvement of TDF on osteoblasts should be taken into account. The aim of this study was to evaluate whether sodium phosphate transporters NPT2A (sodium-dependent phosphate transport protein 2A), NPT2C (sodium-dependent phosphate transport protein 2C), PIT1 (sodium-dependent phosphate transporter 1), and PIT2 (sodium-dependent phosphate transporter 2) were expressed in primary human osteoblasts (HOBs), whether their expression was related to HOBs differentiation and whether TDF could affect mineralization and gene expression. PIT1 and PIT2 were expressed under proliferating conditions and increased after induction of mineralization, while NPT2A and NPT2C were almost undetectable. In HOBs TDF exposure induced a significant dose-dependent decrease in mineralization. Moreover, TDF caused a reduction of COL1A1 and of ATF4 expression in differentiated HOBs. In summary, HOBs do not express NPT2A and NPT2C and do express PIT1 and PIT2, suggesting a role of these two latter in human osteoblast mineralization. TDF impairs osteoblast mineralization, confirming a direct negative effect on bone. Therefore, in clinical practice, bone damage must be suspected and evaluated also in patients receiving TDF without kidney function alterations.

Pathological fractures in a patient with severe osteomalacia and hyperparathyroidism: a multidisciplinary challenge.

Pathological fractures in a patient with severe osteomalacia and hyperparathyroidism: a multidisciplinary challenge.

Osteomalacia with Looser zones caused by celiac disease

Celiac disease is considered a malabsorption syndrome and is characterized by chronicsmall intestinal disease caused by hypersensitivity to the gliadin fraction of gluten. Celiac disease comes with diarrhea, occasional steatorrhea, weight loss, and other complications which might be caused by anemia. Reports of osteomalacia as the only symptom of celiac disease are very rare; however, osteomalacia can be a detected sign of celiac disease. Herein is described a case of osteomalaciawith a Looser zone in a 39-year-old woman who had low bone mineral density caused by severe osteomalacia associated with chronic celiac disease. In patients with pain in the spine and proximal muscle, the risk of osteomalacia should be considered in any kind of diagnosis.

Perioperative management of patients with severe hypophosphataemia secondary to oncogenic osteomalacia: Our experience and review of literature.

Oncogenic osteomalacia (OOM) is a rare paraneoplastic syndrome associated with mesenchymal tumours. It is characterised by phosphaturia, hypophosphataemia, decreased serum Vitamin D3 levels and severe osteomalacia. OOM-inducing tumours are usually benign, arising either from bone or soft tissue, with extremities and craniofacial region being the most common sites. Surgical resection of the tumour remains the mainstay of treatment. Challenges to an anaesthesiologist arise when such patients are planned for surgical resection of the underlying tumour. All the perioperative dilemmas are directly related to the severe hypophosphataemia. We describe three such cases of OOM and their perioperative management.

Severe osteomalacia caused by a phosphaturic mesenchymal tumor secreting fibroblast growth factor 23: a case report

Severe osteomalacia caused by a phosphaturic mesenchymal tumor secreting fibroblast growth factor 23: a case report

Calcium gluconate supplementation is effective to balance calcium homeostasis in patients with gastrectomy.

We demonstrate histological evidence for hyperparathyroidism in patients with gastrectomy. This is, at least in part, explained by impaired calcium absorption, resulting in mineralization defects and secondary hyperparathyroidism. Additionally, we demonstrate improved bone mineralization in patients with gastrectomy after gluconate therapy and showed the effectiveness of calcium gluconate over carbonate to balance impaired calcium hemostasis in mice. Gastrectomy and hypochlorhydria due to long-term proton pump inhibitor therapy are associated with increased fracture risk because of intestinal calcium malabsorption. Hence, our objectives were to histologically investigate bone metabolism in patients with gastrectomy and to analyze the impact of calcium gluconate supplementation on skeletal integrity in the setting of impaired gastric acidification. Undecalcified bone biopsies of 26 gastrectomized individuals were histologically analyzed. In the clinical setting, we retrospectively identified 5 gastrectomized patients with sufficient vitamin D level, who were additionally supplemented with calcium gluconate and had a real bone mineral density (aBMD) follow-up assessments. A mouse model of achlorhydria (ATP4b-/-) was used to compare the effect of calcium gluconate and calcium carbonate supplementation on bone metabolism. Biopsies from gastrectomized individuals showed significantly increased osteoid, osteoclast, and osteoblast indices and fibroosteoclasia (p < 0.05) as well as impaired calcium distribution in mineralized bone matrix compared to healthy controls. Five gastrectomized patients with sufficient vitamin D level demonstrated a significant increase in aBMD after a treatment with calcium gluconate alone for at least 6 months (p < 0.05). Calcium gluconate was superior to calcium carbonate in maintaining calcium metabolism in a mouse model of achlorhydria. Gastrectomy is associated with severe osteomalacia, marrow fibrosis, and impaired calcium distribution within the mineralized matrix. We show that calcium gluconate supplementation can increase bone mineral density in gastrectomized individuals and performs superior to calcium carbonate in restoring calcium/skeletal homoeostasis in a mouse model of achlorhydria.

Severe Osteomalacia Related to Long-Term Intravenous Drug Abuse.

Objective. We present the clinical, biochemical, and imaging findings of a woman with vitamin D deficiency and severe osteomalacia related to intravenous heroin addiction. Results. A 54-year-old woman with a medical history significant for long-standing heroin abuse presented with complaints of bone pain, muscle cramping, and a left hip ulcer. She had been bed bound for approximately 1 year secondary to pain of uncertain etiology, and her husband was bringing her both food and drugs. She was admitted to the hospital for debridement of a right ischial ulcer. Further workup revealed osteomyelitis of the left hip and severe vitamin D deficiency. Radiologic evaluation demonstrated diffuse osteopenia with pseudofractures, as well as true fractures. Conclusion. This is the first case reported in the English literature of advanced osteomalacia resulting from a debilitating narcotic dependency. Vitamin D deficiency should be considered in patients with poor nutrition and prolonged sunlight deprivation from any cause.