Osteoporosis and Kyphoplasty

ABSTRACT

Questions from patients about analgesic pharmacotherapy and responses from authors are presented to help educate patients and make them more effective self-advocates. The topics addressed in this issue are osteoporosis and osteomalacia, with a discussion of conservative management, including kyphoplasty, vertebral augmentation, pain control, and quality of life.     

Oncogenic osteomalacia: Problems in diagnosis and long-term management

Oncogenic osteomalacia is a rare association between mesenchymal tumors and hypophosphatemic rickets. It is more of a biochemical entity than a clinical one. The pathophysiology of the tumor is not clear. However, it has been seen that the clinical and biochemical parameters become normal if the lesion responsible for producing the osteomalacia is excised. For a clinical diagnosis a high index of suspicion is necessary. We present three such cases where in one the oncogenic osteomalacia reversed while in rest it did not. We present this case report to sensitize about the entity.     

Phosphaturic mesenchymal tumor,mixed connective tissue type,non‐phosphaturic variant: Report of a case and review of 32 cases from the Japanese published work

Phosphaturic mesenchymal tumor, mixed connective tissue type (PMTMCT) is a rare neoplasm that can cause tumor‐induced osteomalacia due to overproduction of a phosphaturic hormone, fibroblast growth factor 23 (FGF23). We report here a case of subcutaneous PMTMCT, non‐phosphaturic variant, in the sole. We also review 32 Japanese cases of PMTMCT reported in detail. They occurred in 16 men and 15 women (one was unknown), with ages ranging 20–73 years (median, 48). Tumors were found in soft tissue, bone and sinuses in 17, 11 and four, respectively. A history of long‐standing osteomalacia was noted in all cases except two non‐phosphaturic variant cases. Serum FGF23 level was elevated in 11 of 12 cases examined. In terms of follow‐up information, metastases were found in four patients, and two patients died of disease. In conclusion, PMTMCT is histologically a benign lesion; however, there may be rare metastatic and malignant cases. Wider recognition of the histological features of this unique neoplasm would aid its distinction from the large number of mesenchymal tumors for which it may be mistaken and should enable correct diagnosis of tumors with osteomalacia.     

The development of hypophosphataemic osteomalacia with myopathy in two patients with HIV infection receiving tenofovir therapy

We report two cases in which osteomalacia developed in patients on tenofovir-containing highly active antiretroviral therapy (HAART) in the context of Fanconi syndrome with hypophosphataemia. Bone pain was the presenting feature and myopathy followed in one case. Disability was reversed with withdrawal of the drug and with mineral supplementation. The cases highlight the importance of considering the diagnosis of osteomalacia in patients treated with tenofovir. A possible association with incipient acute renal failure, particularly during nonsteroidal anti-inflammatory drug (NSAID) use, needs further investigation.     

A distinctive patchy osteomalacia characterises Phospho1‐deficient mice

The phosphatase PHOSPHO1 is involved in the initiation of biomineralisation. Bones in Phospho1 knockout (KO) mice show histological osteomalacia with frequent bowing of long bones and spontaneous fractures: they contain less mineral, with smaller mineral crystals. However, the consequences of Phospho1 ablation on the microscale structure of bone are not yet fully elucidated. Tibias and femurs obtained from wild‐type and Phospho1 null (KO) mice (25–32 weeks old) were embedded in PMMA, cut and polished to produce near longitudinal sections. Block surfaces were studied using 20 kV backscattered‐electron (BSE) imaging, and again after iodine staining to reveal non‐mineralised matrix and cellular components. For 3D characterisation, we used X‐ray micro‐tomography. Bones opened with carbide milling tools to expose endosteal surfaces were macerated using an alkaline bacterial pronase enzyme detergent, 5% hydrogen peroxide and 7% sodium hypochlorite solutions to produce 3D surfaces for study with 3D BSE scanning electron microscopy (SEM). Extensive regions of both compact cortical and trabecular bone matrix in Phospho1 KO mice contained no significant mineral and/or showed arrested mineralisation fronts, characterised by a failure in the fusion of the calcospherite‐like, separately mineralising, individual micro‐volumes within bone. Osteoclastic resorption of the uncalcified matrix in Phospho1 KO mice was attenuated compared with surrounding normally mineralised bone. The extent and position of this aberrant biomineralisation varied considerably between animals, contralateral limbs and anatomical sites. The most frequent manifestation lay, however, in the nearly complete failure of mineralisation in the bone surrounding the numerous transverse blood vessel canals in the cortices. In conclusion, SEM disclosed defective mineralising fronts and extensive patchy osteomalacia, which has previously not been recognised. These data further confirm the role of this phosphatase in physiological skeletal mineralisation.     

Acquired Fanconi Syndrome in a Patient with Nontyphoidal Salmonella Bacteremia

Nontyphoidal Salmonella is a common cause of bacterial gastroenteritis, occasionally causing bacteremia. We herein report the case of an 80-year-old man who presented with bacteremia and pre-renal acute kidney injury (AKI) secondary to diarrhea caused by nontyphoidal Salmonella. Despite AKI improvement on fluid administration, some serological abnormalities, such as hypokalemia, hypophosphatemia, and hypouricemia, and abnormal urinary findings emerged, including renal glycosuria and aminoaciduria. Fractional excretion of phosphate and uric acid was increased, suggesting that the serological and urinary abnormalities may have arisen from Fanconi syndrome. Physicians should consider acquired Fanconi syndrome when patients with nontyphoidal Salmonella bacteremia present with electrolyte disorders.     

Tumor-induced osteomalacia with elevated fibroblast growth factor 23: a case of phosphaturic mesenchymal tumor mixed with connective tissue variants and review of the literature

Tumor-induced osteomalacia (TIO), or oncogenic osteomalacia (OOM), is a rare acquired paraneoplastic disease characterized by renal phosphate wasting and hypophosphatemia. Recent evidence shows that tumor-overexpressed fibroblast growth factor 23 (FGF23) is responsible for the hypophosphatemia and osteomalacia. The tumors associated with TIO are usually phosphaturic mesenchymal tumor mixed connective tissue variants (PMTMCT). Surgical removal of the responsible tumors is clinically essential for the treatme...