Improvement of Giant Cell Lesions of the Jaw Treated With High and Low Doses of Denosumab: A Case Series.

Giant cell tumors (GCTs) and central giant cell granulomas (CGCGs) are aggressive lesions that appear in the jaw. These lesions occur in the second and third decades of life and often arise in the mandible. Clinical manifestations of these lesions vary from asymptomatic to symptomatic tooth displacement with cortical perforation. GCTs, which are characterized by multinucleated osteoclast-type giant cells that express receptor activator of nuclear factor-κB (RANK) ligand, rarely present in the jaw and have overlapping histopathologic features with CGCGs, which are composed of fibroblastic stromal cell lesions. GCTs and CGCGs have overlying histopathologic features that make distinction between the two challenging. There is a real controversy as to whether giant cell tumors and central giant cell granulomas are in fact, one and the same lesion. The majority of GCTs occur in the long bone, with surgery being the typical therapeutic option. Denosumab as a treatment modality is a fairly new concept that has been used effectively in GCTs affecting long bones. There is less experience, however, with its use for jaw lesions. This seven-case series describes the effective use of both low-dose and high-dose denosumab in the treatment of GCTs and CGCGs affecting the jaw and special dosing considerations for younger patients who present with disease. © 2017 The Authors. JBMR Plus Published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.

Hypercalcemia of Malignancy and Colorectal Cancer.

Our aim is to describe the association between colorectal cancer (CRC) and humoral hypercalcemia of malignancy (HHM). Causes of hypercalcemia of malignancy include parathyroid hormone-related peptide (PTHrP) secretion, local osteolysis, calcitriol production and ectopic parathyroid hormone (PTH) secretion. Hypercalcemia of malignancy in patients with CRCs is a rare scenario. A patient with anal squamous cell carcinoma was admitted with hypercalcemia, suppressed PTH and hypophosphatemia. He was found to have metastatic anal squamous cell carcinoma to the liver. Further evaluation revealed elevated PTHrP and 1,25-dihydroxyvitamin D and low 25-hydroxyvitamin D. Over a 5-month course, the hypercalcemia responded poorly to bisphosphonates, transiently to prednisone, but showed marked improvement with chemotherapy. A review of English language publications in Pubmed and a reference search of retrieved articles revealed 29 cases of CRC causing PTHrP-mediated hypercalcemia. Most patients were middle-aged men (mean ± SD: 56.7 ± 13.4 years), with advanced metastatic cancer (85% with hepatic metastasis) and severe hypercalcemia (mean ± SD: 15.6 ± 1.9 mg/dL, 62% with Ca > 14). This condition is associated with high mortality (79%) and short survival (median 54.5 days, CI: 21 - 168). Despite being uncommon, HHM (PTHrP-mediated) should be considered in patients with metastatic CRC presenting with hypercalcemia. Clinicians should be aware that combined etiologies may be present, particularly in cases of resistant hypercalcemia. Treatment of the underlying malignancy is essential for calcium control.

Indications and Outcomes of Osteoporosis and Bone Modulation Therapies.

Osteoporosis is a disorder of bone strength that leads to an increased risk of fractures. It is most commonly seen in patients aged 50 or older, although it can sometimes occur at a younger age if there are other comorbidities present. The most common cause of osteoporosis by far is menopause, although it also occurs in men, usually with higher morbidity rates than those seen in women. There are many treatment options available, such as anabolics and antiresorptives, with many more currently being developed. However, osteoporosis remains grossly unrecognized and untreated, resulting in a significant strain on the American economy.

Antiresorptive Therapies for Osteoporosis.

Osteoporosis is a disease of low bone density, translating to increased fragility and risk for fracture. It is a significant public health problem that is widely undertreated, despite the many options of treatment available. Among these, the most effective are the antiresorptive medications, such as bisphosphonates. There is an abundance of evidence about the efficacy and safety profile of these medications. However, there is mounting evidence that, after 10 years on treatment with a bisphosphonate, patients are at a higher risk of developing some of the serious side effects of atypical femur fractures and osteonecrosis of the jaw.

Osteoporosis as the sole manifestation of systemic mastocytosis in a young man.

OBJECTIVE: To highlight the difficulty involved in making a diagnosis of systemic mastocytosis (SM) when it manifests solely as osteoporosis. METHODS: We present a detailed case report and review the literature regarding the work-up of secondary osteoporosis and the diagnosis and treatment of SM. Other cases of SM presenting as osteoporosis in male patients are also described. RESULTS: A 35-year-old man presented with back pain after weight lifting and was diagnosed with a T7 vertebral compression fracture. A dual-energy x-ray absorptiometry scan resulted in a T-score of -3.2 in the spine and of -1.9 and -2.4 in the hip and femoral neck areas, respectively. Results of standard tests for secondary osteoporosis including calcium, phosphorus, 25-hydroxyvitamin D, kidney and liver function, thyroid function, testosterone level, and midnight salivary cortisol were normal. Further testing revealed a high serum tryptase level of 26.8 µg/L (reference range, <11.4) and elevated urinary histamine at 39.1 µg/g creatinine (reference range, <35). Bone marrow biopsy confirmed the diagnosis of mastocytosis. CONCLUSION: The rare diagnosis of SM is difficult when there is little clinical suspicion and remains a challenge to endocrinologists and other physicians. The condition should be suspected in young male patients with no other obvious cause of osteoporosis.

Osteoporosis and gastrointestinal disease.

Gastrointestinal disease is often overlooked or simply forgotten as a cause of osteoporosis. Yet, the consequences of osteoporotic fractures can be devastating. Although the bulk of the published experience regarding osteoporosis is derived from the postmenopausal population, this review will focus on gastrointestinal disorders implicated in osteoporosis, with an emphasis on inflammatory bowel disease and celiac disease. The unique aspects of gastrointestinal diseases associated with osteoporosis include early onset of disease (and, therefore, prolonged exposure to risk factors for developing osteoporosis, particularly with inflammatory bowel disease and celiac disease), malabsorption, and maldigestion of nutrients necessary for bone health and maintenance (eg, calcium, vitamin D), as well as the impact of glucocorticoids. These factors, when added to smoking, a sedentary lifestyle, hypogonadism, and a family history of osteoporosis, accumulate into an imposing package of predictors for osteoporotic fracture. This paper will review the identification and treatment strategies for patients with gastrointestinal disorders and osteoporosis.

Correlates of low bone density in females with anorexia nervosa.

UNLABELLED: The objectives were to delineate those factors which correlate with low bone density in patients with anorexia nervosa and in turn to predict those at greatest risk for osteopenia. DESIGN: Bone density was evaluated by dual energy x-ray absorptiometry in 28 postmenarchal females with anorexia nervosa who had never received hormonal therapy. Bone density results were correlated with specific historical and physical factors utilizing descriptive statistics, scatter plots, and the Spearman correlation coefficient. RESULTS: Mean age was 18.6 years, mean age at menarche was 12.9 yrs, mean length of illness was 19.8 months and mean duration of amenorrhea was 13.4 months. Mean % ideal body weight was 84% at the time of bone density, 75% at minimum weight and 100% at maximum weight. Mean lumbar spine bone density was -1.69 standard deviations from the norm; mean lateral spine bone density was -1.45 standard deviations from the norm; mean femoral neck of the hip bone density was -1.18 standard deviations from the norm. There was a strong negative correlation between duration of amenorrhea and bone density at the lumbar spine (r = -0.50, p < .01) and a mild correlation at the lateral spine (r = -0.49, p < 0.05) and femoral neck (r = -0.41, p < 0.05). There was also a strong negative correlation between length of illness and bone density at the lumbar spine (r = -0.53, p < 0.01) and lateral spine (r = -0.77, p < 0.0001), and a mild correlation with the femoral neck (r = -0.48, p < 0.05). Scatter plots of lumbar bone density versus duration of amenorrhea, and versus length of illness clearly showed not only that longer duration of amenorrhea and longer length illness correlated to bone loss, but also strikingly that within a short time of being ill and amenorrheic, significant bone loss was seen. Age, and age at menarche correlated mildly with osteopenia at the lateral spine; age correlated mildly with osteopenia at the femoral neck as well. There was a trend for minimum BMI to correlate with osteopenia at the lateral spine. There were no correlations of bone density with % IBW at bone density, minimum % IBW, maximum % IBW, change in % IBW, BMI at the time of the bone density, maximum BMI or change in BMI. CONCLUSIONS: Low bone density, especially in the lumbar spine, correlated with both a longer duration of amenorrhea and longer length of illness, but not with other factors, in our patients with anorexia nervosa. As many of these patients, even those with a short duration of illness and amenorrhea, were osteopenic, it is advisable to continue to perform bone density studies in all patients with anorexia nervosa, on both a clinical and research basis.