Participants and study design
fracture, endocrine disorders, osteoporosis
BOWEL DISORDERS, HYPERTHYROIDISM, PRIMARY HYPERPARATHYROIDISM, ENDOCRINE DISORDERS, OSTEOPOROSIS
The vitamin K in osteoporosis trial was an 18 month randomised controlled trial (RCT) conducted in 105 ambulatory post-menopausal women with osteoporosis (PMO) aged between 55–85 years. Participants who had been on oral bisphosphonate and/or calcium/vitamin D supplements for fracture prevention for at least 12 months were invited to take part in the study. Exclusion criteria included secondary osteoporosis such as inflammatory joint or bowel disorders, current glucocorticoid therapy, chronic kidney disease stage 4 and 5, malabsorption, untreated endocrine disorders (primary hyperparathyroidism, hyperthyroidism) or current or past treatment (< 12 months) with other osteoporosis drugs e.g. teriparatide, denosumab, hormone replacement therapy or selective oestrogen receptor modulators and treatment with vitamin K antagonists; warfarin. Participants were recruited from April 2015 to September 2018 from the metabolic bone clinics, the osteoporosis unit at Guy’s Hospital, primary care or through community advertising and public engagement activities as previously described [Ethical approval was obtained by the National Research Ethics Service (NRES Committee London—Westminster), approval number10/H0802/72. The trial was conducted according to the protocol and in compliance with the principles of the Declaration of Helsinki, the principles of Good Clinical Practice (GCP) and in accordance with Medicines for Human Use (Clinical Trials) Regulations. The trial protocol and substantial amendments were reviewed and approved by the United Kingdom (UK) Medicines and Healthcare products Regulatory Agency (MHRA). The trial was registered with the European Union Drug Regulating Authorities Clinical Trials Database (EudraCT) (registration number 2010–02258712) and on the ClinicalTrials.gov registry (ID; NCT01232647).The trial was designed in 2 stages. The first stage was a pre-screening study of up to 374 with PMO on oral bisphosphonate to assess their serum vitamin KAll 3 groups were advised to continue with their standard treatment of oral bisphosphonate and vitamin D (800 IU/day) if their dietary calcium intake was satisfactory (> 1 g/day) or combined calcium/vitamin D supplements (1.0 g calcium and 800 IU vitamin D/day) if their dietary calcium intake was low (< 500 mg/day). A detailed clinical history and examination were done at baseline. BMD and routine blood tests were measured at baseline and at 18 months. Bone turnover markers and serum vitamin KPrimary outcomes were changes in BMD at the lumbar spine (LS), femoral neck (FN) and total hip (TH) at 18 months between the 2 treatment arms (vitamin KFlowchart illustrating the study protocol