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Denosumab is a new biological (monoclonal antibody) antiresorptive treatment of osteoporosis which is administrated as a subcutaneous 60 mg injection twice a year. Compared with placebo, three years of treatment increases bone mineral density by 6-9% and decreases the risk of vertebral and hip fractures by 68% and 40%, respectively, in postmenopausal women with osteoporosis. In men with iatrogenic hypogonadism due to prostate cancer, the risk of vertebral fractures is decreased by 62%. Side effects are few, but the treatment may increase risk of infections.

Drugs can affect the skeleton in different ways. Antiepileptic drugs were not associated with any major fracture risk. Lithium was associated with a decreased fracture risk. Insulin, sulphonylureas and metformin were associated with a decreased risk, whereas glitazones were associated with an increased risk. Blood pressure lowering drugs, thiazide diuretics and nitroglycerin were associated with a decreased risk of fractures, whereas amiodarone and loop diuretics were associated with an increased risk. Pain medication varied from no effect to an increased fracture risk.

The incidence of hip fractures has been increasing throughout the world including the Nordic countries. The aim of this study was to examine if there is a similar trend in Denmark.Statistics from the National Hospital Discharge Register on the number of patients with at least one occurrence of hip fracture in the years 1977 to 1999 compared to the number of inhabitants in Denmark (numbers from Statistics Denmark).The total number of patients with at least one hip fracture increased from approximately 6,500 in 1977 to approximately 11,000 in 1999. Since approximately 1995 the number has been relatively stable. The largest absolute increase was among women (from 4,800 to 9,000 per year), while a smaller absolute but large relative increase was seen among men (from approximately 1,600 to 3,200 per year). The incidence rates increased among men below the age of 50 years, while a more moderate increase was observed among women below the age of 50. The incidence rates remained relatively stable among men and women aged 50 to 69 years, while a limited increase was observed among women aged 70 to 79 years. Among men and women above the age of 80, the incidence rates increased until approximately 1992, followed by stagnation.The number of hip fractures increased up to approximately 1995 in Denmark followed by stagnation. In view of the large number of hip fractures, a multi-pronged strategy including general practice, primary nursing care, nursing homes, orthopaedic surgeons, and medical specialties is needed in order to reduce the number of hip fractures.

Three recently published randomized controlled studies on the effects of calcium and vitamin D on fracture risk from the UK and the USA were critically reviewed. We found problems related to their external validity compromising their transferability to Denmark. Furthermore, study power was limited because of the selection of low-risk patients, problems with compliance and persistence, and supplementation with calcium and vitamin D outside the protocol. Two recent meta-analyses including the three studies supported the continuous use of calcium and vitamin D to prevent fractures in the elderly.

Active vitamin D increases the differentiation and exerts antiproliferative effects in cancer cells. Recent data suggest that vitamin D is activated locally in cancer cells. Ecologic studies have shown an inverse correlation between breast cancer mortality and sun exposure and dietary vitamin D intake. In clinical studies an impaired vitamin D status is associated with a 20-30% increased breast cancer incidence and 10-20% increased mortality. As vitamin D insufficiency is common, it is important to clarify whether vitamin D status affects the risk and prognosis of breast cancer.

Cinacalcet is a new drug with antiparathyroid effects that belongs to the class of calcimimetics. It increases the sensitivity of the calcium-sensing receptor (CaSR) to calcium, thus inducing a decrease in plasma parathyroid (PTH) levels. In patients with uncontrolled secondary hyperparathyroidism due to uremia, cinacalcet has been shown to decrease the levels of PTH even in those optimally treated with calcium and 1-ahydroxylated vitamin D. Cinacalcet decreases plasma calcium and plasma PTH levels in patients with primary hyperparathyroidism or parathyroid cancer.

Strontium ranelate (SR) is a new drug for osteoporosis that has a unique effect profile, being antiresorptive as well as anabolic. In postmenopausal women with spinal osteoporosis pretreated with calcium and vitamin D, SR reduced the risk of new vertebral fractures after 1 year by 49% and after 3 years by 41% (NNT = 9). The numbers of clinical fractures were in the same periods reduced by 52% and 38%, respectively. The number of patients with more than one new spinal fracture was reduced by 36%. Height reduction was less among the patients so treated, and there was a tendency towards less lumbar pain. Measured lumbar BMD increased 14.4% over three years, corresponding to an increase of 6.8% after adjustment for bone strontium content, compared with a decrease in the placebo group of 1.3%. The risk of new non-vertebral fractures was reduced by 16%. Among elderly women with a hip T-score-3, SR decreased the risk of hip fractures by 36% over three years (NNT = 48). In patients with osteopenia and at least one clinical risk factor, SR reduced the risk of first vertebral fracture by 72% over three years (NNT = 12). In patients over 80 years of age, the risk of new vertebral fractures was reduced by 32% (NNT = 14). There were few side effects. SR is thus suitable for reducing the risk of vertebral and hip fractures from postmenopausal osteoporosis, especially among patients with upper abdominal dyspepsia and the elderly.