severe vitamin D deficiency. These includes subperiosteal resorption of the phalanges, bone cysts, and resorption of the distal ends of long bones such as the clavicle and humerus. More severe osteomalacia can lead to shortening and bowing of the tibia, pathologic fractures, coxa profunda hip deformity. Coxa profunda is a non-specific finding and refers to a deep acetabular socket. Image 2: Coxa profunda (pincer type femoroacetabular impingement). Image from radiopedia.org
63
primary hyperparathyroidism. Consideration may be given to DXA, especially if the patient has other risk factors for bone loss. Conclusions
TEST
and they advise treating all Osteomalacia is a metabolic bone patients with vitamin D levels disease that can have profound below 25nmol/l and also those consequences especially on with levels between 25-50nmol/l the older population if fracture who have risk factors including ensues. Increased awareness of fragility fracture, osteoporosis, vitamin D’s role in metabolic bone symptoms suggestive of vitamin disease is a useful tool to prevent D deficiency, reduced UV this disease. It is clear the Irish exposure, raised parathyroid population have a significant risk of Image 2: Coxa Features profunda (pincer type femoroacetabular impingement). Image from radiopedia.org assessment. Transiliac bone biopsy Radiological hormone, on treatment with vitamin d deficiency due to many should be completed by a skilled anticonvulsants or glucocorticoids factors such as latitude, reduced X-ray remains the most important professional. It is preferred as it Histological Diagnosis or malabsorption.4 Vitamin D sunlight exposure and dietary imaging technique for metabolic 12 is a relatively accessible site. A levels should ideally be checked intake. Patients with a vitamin D bone disease. The most common definite diagnosis of osteomalacia one for month after replacement. If level Although routinely performed bone biopsy is the gold standard diagnosis of osteomalacia. It below 25nmol/l should have radiographicnot abnormality is cortical requires an osteoid volume of abnormalities persist with calcium replacement therapy and those thinning but this is a non-specific >10% along with evidence of may be useful if the diagnosis remains unclear after clinical, laboratory and radiological assessment. levels, rechecking PTH can be with a level between 50nmol/l finding and these are generally decreased mineralization as useful as often replacing vitamin should also be treated if they have Transiliac bone biopsy should be completed by a skilled professional. It is preferred as it is a not to be relied upon for definitive assessed by tetracycline double D can unmask concomitant risk factors. 5 diagnosis. Looser zones also Double-labelling of the labelling. relatively accessible site (12). A definite diagnosis of osteomalacia requires an osteoid volume of known as cortical infarctions, bone with tetracycline should be Vitamin D and Bone Health: >10% along evidence of decreased assessed by tetracycline double labelling milkman’s lineswith or pseudofractures completedmineralization before the bone as biopsy A Practical Clinical Guideline for Patient Management are lucencies that extend part is performed. This involves giving (5). Double-labelling of the bone with tetracycline should be completed before the bone biopsy is (for use in conjunction with full guideline) The quick guide way through the bone usually at two doses of tetracycline 10-14 performed. involves giving two doses of tetracycline 10-14 days apart. The amount of bone a right angle toThis the cortex. They days apart. The amount of bone • Patients with diseases with outcomes that may be improved with vitamin D treatment e.g. confirmed are a type of insufficiency fracture formed during that period osteoporosis formed during that period can be calculated from the can distance between theosteomalacia, double bands of that strongly favour the diagnosis be calculated from the distance • Patients with symptoms that could be attributed to vitamin D deficiency e.g. suspected osteomalacia, chronic widespread pain with other features of osteomalacia tetracycline labels during histologic evaluation (12). when they are fluorescence present bilaterally between the double bands of • Before starting patients on a potent antiresorptive agent (zoledronate or denosumab or teriparatide) in a symmetric pattern and in a tetracycline fluorescence labels classic location such as the axillary during histologic evaluation.12 25(OH) vitamin D (nmol/L) border of the scapulae, ribs, or 25-50 <25 Treatment of Vitamin D >50 posterior ulnae. Other frequently Deficiency involved sites include the superior
Histological Diagnosis Although not routinely performed bone biopsy is the gold standard for diagnosis of osteomalacia. It may be useful if the diagnosis remains unclear after clinical, laboratory and radiological References 1. Workshop consensus for vitamin D nutritional guidelines . al, Norman et. s.l. : Journal of Steroid Biochecmistry and Molecular Biology, 2007, Vol. 103; 204-5 2. Vitamin D deficiency in Europe: pandemic? al, Cashman et. s.l. : American Journal of Clinical Nutrition, 2016, Vol. 103(4); 957-8 3. Vitamin D status of Irish adults: findings from the National Adult. al, Cashman et. Cork : British Journal of Nutrition, 2012, Vol. 109; 1246-56 4. Vitamin D and bone health: A practical clinical guide for patient management.
5.
6.
7.
Society, Royal Osteoporosis. s.l. : Guidelines , 2019. Osteomalacia - What the rheumatologist needs to know. al, Arya et. s.l. : Indian Journal of Rheumatology, 2007, Vol. 2; 1722. O1. Osteomalacia: The missing link in the pathogenesis of bisphosphonate related osteonecrosis of the jaw? . al, Bedogni et. 2012, Oncologist, pp. 17(8);1114-9. Osteomalacia revisited. al, Gifre et. s.l. : Clinical Rheumatology, 2010, Vol. 30; 639-45.
INTERPRET
If one or more of following applies: • Fragility fracture/osteoporosis/ high fracture risk • Drug treatment for bone disease • Symptoms suggestive of vitamin D deficiency • Increased risk of developing vitamin D deficiency e.g. • Reduced UV exposure • Raised PTH • Treatment with anticonvulsants or glucocorticoids • Malabsorption
Maintain vitamin D through safe sun exposure and diet
Treat
Treat Rapid correction if:
TREAT
Other radiographic changes can include those related to secondary hyperparathyroidism from severe vitamin D deficiency. These includes subperiosteal resorption of the phalanges, bone cysts, and resorption of the distal ends of long bones such as the clavicle and humerus. More severe osteomalacia can lead to shortening and bowing of the tibia, pathologic fractures, coxa profunda hip deformity. Coxa profunda is a non-specific finding and refers to a deep acetabular socket.
25 hydroxycholecalciferol (25(OH-D)) although biologically inert until converted to 1,25 hydroxycholecalciferol remains the best measurement of overall vitamin D reserves as the half-life of the active form is <4 hours.13 The Endocrine Society classifies vitamin D deficiency as a level below 25nmol/l and vitamin D insufficiency as a level below 30nmol/l.14 They recommend that deficient adults are treated with 50,000 IU of Vitamin D2 or D3 once a week for 8 weeks or 6000 IU per day for the same time period. This is available in a variety of preparations. This should be followed by maintenance therapy of 1500-2000 IU/day. The aim is to achieve a blood level of 25(OH) D above 30nmol/l. In patients with obesity or malabsorption syndromes they suggest a dose two or three times higher for replacement and a maintenance dose of 3000-6000 IU/day.13 The Royal Osteoporosis Society give similar recommendations
HOW TO TREAT VITAMIN D DEFICIENCY
• Symptoms of vitamin D deficiency • About to start treatment with potent antiresorptive agent (zoledronate or denosumab or teriparatide)
CAUTION
• Approximately 300,000 IU vitamin D3 (or D2) orally in divided doses over 6-10 weeks • Commence maintenance vitamin D 4 weeks after loading as per elective correction*
Elective correction in all other instances
*
• When co-prescribing vitamin D supplements with an oral antiresorptive agent, maintenance therapy may be started without the use of loading doses.
FOLLOW UP
and inferior pubic rami, and proximal medial femur. True fractures may occur through these weakened sites.11
• 800-2,000 IU vitamin D3 daily or intermittently at higher equivalent dose
• Check serum adjusted calcium one month after treating with loading doses of vitamin D. Vitamin D repletion may unmask primary hyperparathyroidism • Routine repeat vitamin D testing is generally unnecessary Example regimens are given in Appendix 1 of the full guideline
Image 3: Royal Osteoporosis Society Guidelines on Vitamin D treatment. Published online in guidelines.co.uk by Royal Osteoporosis Society “ROS Vitamin D and Bone health Guideline” March 2019. 8.
Aetiology and clinical profile of osteomalacia. al, Rajeswari et. s.l. : National Medical Journal of India, 2003, Vol. 16; 139-142. 9. al, Lips et. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. s.l. : John Wiley & Sons, 2013. 10. Osteomalacia due to vitamin D depletion: a neglected consequence of intestinal malabsorption. al, Basha et. s.l. : American Medical Journal, 2000; 296-300. 11. Resnick. Diagnosis of bone and joint disorders; 2670 12. Bone densitometry and bone biopsy. al,
Ralston et. s.l. : Best Practice Clinical Rheumatology, 005, Vol. 19; 487-501 13. Vitamin D deficiency. Holick. s.l. : New England Journal of Medicine, 2007, Vol. 357; 266-281 14. Evaluation, Treatment, and Prevention of Vitamin D Deficiency: an Endocrine Society Clinical Practice Guideline. al, Holick et. 7, s.l. : Journal of Endocrinology and Metabolism, 2011, Vol. 96; 1911-30 15. The Role of Vitamin D in Cancer Prevention. al, Garland et. 96(2), s.l. : American Journal of Public Health, 2006; 252-61
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