Critical reappraisal of vitamin D deficiency

The current surge of interest in vitamin D is fuelled not only by evidence that vitamin D supplementation decreases the risk of osteoporotic fractures but also by vast observational studies indicating a variety of beneficial extraskeletal effects (including decreases in the risks of cancer, inflammatory diseases, and even death). Serum 25-hydroxyvitamin D (25(OH)D) assay is now a highly reliable method for evaluating vitamin D stores in individual patients. Nevertheless, the normal or desirable 25(OH)D range for patients seen in everyday clinical practice needs to be more accurately defined. Maintaining serum 25(OH)D above 75 nmol/L is currently recommended to ensure optimal bone health, but higher levels may be required to obtain some of the extraskeletal benefits. Naturally occurring vitamin D is by far the most widely used form for correcting vitamin D deficiency, and the hydroxylated derivatives have only a few highly specific indications. However, controversy persists about the optimal modalities of natural vitamin D supplementation in terms of the type of vitamin (D2 or D3), schedule (once daily or at wider intervals), and route (oral or injectable). For chronic supplementation to protect against bone loss, a daily dosage of at least 800 IU seems required. Higher dosages (e.g., 100,000 to 200,000 IU every 2 months for 6 months) may be needed to correct established vitamin D deficiency; a repeat 25(OH)D assay after 4 to 6 months may help to assess the treatment response and to adjust the subsequent vitamin D dosage. The current emphasis is on the detection of vitamin D deficiency in the general population and in subgroups at risk for osteoporosis followed by an assessment of severity and the initiation of appropriate treatment. From a public health perspective, supplying at least 800 IU per day seems useful and safe

Hypophosphatasie : diagnostic et conduite à tenir

International audienc

Rachitismes et ostéomalacies à l’âge adulte

La principale cause de l’ostéomalacie chez l’adulte est la déficience sévère et prolongée en vitamine D, facilement reconnue aujourd’hui par le dosage de la 25-hydroxyvitamine D [25(OH)D]. Le contexte clinique, des anomalies biologiques phosphocalciques, des anomalies sur les examens d’imagerie (radiographies standard, scintigraphie osseuse), une densité parfois très basse mesurée en densitométrie osseuse, permettent d’évoquer la possibilité d’un trouble de la minéralisation de type ostéomalacique, diagnostic éventuellement confirmé par les données histomorphométriques de la biopsie osseuse trans-iliaque après double marquage aux cyclines. Une cause à la carence en vitamine D doit être recherchée et traitée. La supplémentation simple en vitamine D permet de guérir les patients. Des formes rares d’ostéomalacie, dénommées rachitismes vitamino-D-résistants (dépendants, type 1 et 2), sont dues à une anomalie génétique enzymatique (rachitisme pseudo-carentiel de Prader ou rachitisme vitamino-D-résistant de type 1, lié à un déficit en 1-alpha hydroxylase) ou à une anomalie du récepteur à la vitamine D (VDR ; rachitisme vitamino-D-dépendant de type 2) créant une résistance des organes cibles à l’action de la vitamine D. Dans cette dernière forme, le traitement est difficile, nécessitant le recours à des doses pharmacologiques fortes de vitamine D, en complément de la forte supplémentation calcique

What do we know about atypical femoral fractures? Insights and enigmas

Although the existence of atypical femoral fractures is well established and bisphosphonate therapy is thought to be a major risk factor, the underlying mechanisms are poorly understood. Epidemiological data show that atypical femoral fractures account for only a small proportion of diaphyseal subtrochanteric femoral fractures, being about 100 times less common than proximal femoral fractures. Consequently, the existence of atypical femoral fractures does not call into question the extremely favorable risk/benefit ratio of bisphosphonate therapy in patients with osteoporosis. Clearly, the number of fractures prevented by bisphosphonate therapy far exceeds the number of atypical femoral fractures potentially related to bisphosphonates

Ultrastructural characteristics of glucocorticoid-induced osteoporosis

International audienc

Extraspinal sciatica revealing late metastatic disease from parotid carcinoma

Sciatica is a clinical symptom usually caused by a disk herniation and less often by other conditions such as tumors, infections, or inflammatory diseases. We report the case of a woman in whom sciatica led to the identification of a large pelvic metastasis from a carcinoma of the parotid gland

Osteomalacia in a patient with Paget's bone disease treated with long-term etidronate

SummaryA 93 year-old woman with Paget\u27s disease of bone had been treated with etidronate without interruption during 20 years. The daily dose was usual (5 mg/kg/day) but this prescription had never been stopped by her physicians. Two fractures had already occurred in pagetic (right tibia) and non pagetic bones (right fibula) within the last 2 years, and she presented rib fractures, another right tibia fracture and right femur fracture during hospitalization time. X-rays films showed major osteolysis of left ulna and right tibia. Blood samples and technetium bone scan brought no evidence for sarcoma or lytic evolution of the disease. A transiliac bone biopsy on non pagetic bone site confirmed the diagnosis of osteomalacia (increased osteoid parameters), with secondary hyperparathyroidism (hook resorption). In Paget\u27s disease of bone, continuous treatment by etidronate may induce generalized osteomalacia, and increase the risk of fracture in both pagetic and non-pagetic bones. Whereas physicians and pharmaceutical industry try to improve the observance of those drugs, this striking observation also points out that a prescription always needs to be updated

Is androgen therapy indicated in men with osteoporosis?

Male osteoporosis is not rare, and its management is a public health issue. The clinical evaluation must include investigations for one or more etiological factors such as hypogonadism, which is found in 5% to 15% of men with osteoporosis. Gradual development of moderate hypogonadism is the most common situation, and the prevalence of hypogonadism increases with advancing age. The wealth of scientific data establishing a major role for sex hormones in growth, bone turnover, and the osteoporotic fracture risk is in striking contrast to the paucity of therapeutic trials. Androgen therapy did not consistently produce bone mass gains, and no data on potential anti-fracture effects are available. Androgen therapy was not associated with significant increases in mortality, prostate disorders, or cardiovascular events, but few data were obtained in patients older than 75 years. In practice, in a male patient with osteoporosis, a diagnosis of marked and persistent hypogonadism requires investigations for treatable causes. In patients younger than 75 years of age, androgen replacement therapy should be started, in collaboration with an endocrinologist. A history of fractures indicates a need for additional osteoporosis pharmacotherapy. The risk/benefit ratio of androgen therapy is unclear in men older than 75 years, in whom a reasonable option consists in combining fall-prevention measures, vitamin D supplementation, and a medication proven to decrease the risk of proximal femoral fractures

Monoclonal gammopathy of undetermined significance, multiple myeloma, and osteoporosis

The finding of monoclonal gammopathy of undetermined significance (MGUS) is not infrequent during an evaluation for osteoporosis or a fracture. In most cases, the diagnosis is MGUS, whose prevalence increases with age. Although the impact of MGUS on bone mineral density, bone remodeling, and the fracture risk remains unclear, this asymptomatic hematological disorder may constitute a risk factor for osteoporosis. Furthermore, each year, 1% of patients with MGUS progress to multiple myeloma, a disease whose pathophysiology and association with bone loss and pathological fractures are increasingly well understood. Osteoporotic fractures, although probably common in myeloma patients, are less likely to be recognized. Here, we discuss the pathophysiology of myeloma and MGUS and their impact in terms of bone mineral density, osteoporotic fractures, and bone turnover markers