Extraskeletal benefits and risks of calcium, vitamin D and anti-osteoporosis medications.
Drugs used for the prevention and the treatment of osteoporosis exert various favourable and unfavourable extra-skeletal effects whose importance is increasingly recognized notably for treatment selection.


BACKGROUND
The therapeutic armamentarium for the prevention and the treatment of osteoporosis is increasingly large, and possible extra-skeletal effects of available drugs could influence the choice of a particular compound.


METHODS
The present document is the result of a national consensus, based on a systematic and critical review of the literature.


RESULTS
Observational research has suggested an inverse relationship between calcium intake and cardiovascular diseases, notably through an effect on blood pressure, but recent data suggest a possible deleterious effect of calcium supplements on cardiovascular risk. Many diverse studies have implicated vitamin D in the pathogenesis of clinically important non-skeletal functions or diseases, especially muscle function, cardiovascular disease, autoimmune diseases and common cancers. The possible effects of oral or intravenous bisphosphonates are well-known. They have been associated with an increased risk of oesophageal cancer or atrial fibrillation, but large-scale studies have not found any association with bisphosphonate use. Selective oestrogen receptor modulators have demonstrated favourable or unfavourable extra-skeletal effects that vary between compounds. Strontium ranelate has a limited number of non-skeletal effects. A reported increase in the risk of venous thromboembolism is not found in observational studies, and very rare cases of cutaneous hypersensitivity reactions have been reported. Denosumab has been introduced recently, and its extra-skeletal effects still have to be assessed.


CONCLUSIONS
Several non-skeletal effects of bone drugs are well demonstrated and influence treatment choices.
Department of Medicine, CHU Brugmann, Université Libre de Bruxelles, Brussels, Belgium.
J-J
JJ
Body
P
P
Bergmann
S
S
Boonen
J-P
JP
Devogelaer
E
E
Gielen
S
S
Goemaere
J-M
JM
Kaufman
S
S
Rozenberg
J-Y
JY
Reginster
D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D050071:Bone Density Conservation Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002118:Calcium / Q000494:pharmacology / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000139:chemically induced; D032921:Consensus; D000069448:Denosumab; D019587:Dietary Supplements / Q000009:adverse effects; D004164:Diphosphonates / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000187:drug effects; D009369:Neoplasms / Q000139:chemically induced; D009942:Organometallic Compounds / Q000494:pharmacology; D010024:Osteoporosis / Q000188:drug therapy*; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology / Q000627:therapeutic use*; D020521:Stroke / Q000139:chemically induced; D013876:Thiophenes / Q000494:pharmacology; D014807:Vitamin D / Q000494:pharmacology / Q000627:therapeutic use*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D009942:Organometallic Compounds; D020845:Selective Estrogen Receptor Modulators; D013876:Thiophenes; C081587:strontium ranelate; D014807:Vitamin D; D000069448:Denosumab; D002118:Calcium