Clinical Investigations The Effect of Calcium and Vitamin D 3 Supplementation on the Healing of the Proximal Humerus Fracture: A Randomized Placebo-Controlled Study A. M. Doetsch, 1 J. Faber, 2 N. Lynnerup, 3 I. Wa¨tjen, 1 H. Bliddal, 1 B. Danneskiold–Samsøe 1 1 Parker Institute, Frederiksberg Hospital, Copenhagen, Denmark 2 Department of Endocrinology E, Frederiksberg Hospital, Copenhagen, Denmark 3 Panum Institute, University of Copenhagen, Copenhagen, Denmark Received: 6 July 2003 / Accepted: 30 January 2004 / Online publication: 16 June 2004 Abstract. Thepurposeofthisstudywasto(1)quantify thehealingprocessofthehumanosteoporoticproximal humerus fracture (PHF) expressed in terms of callus formationoverthefractureregionusingBMDscanning, and(2)quantifytheimpactofmedicalinterventionwith vitamin D 3 and calcium on the healing process of the humanosteoporoticfracture.Theconservativelytreated PHFwaschoseninordertofollowthegenuinefracture healing without influence of osteosynthetic materials or casts. Thirty women (mean age = 78 years; range = 58–88) with a PHF, osteoporosis or osteopenia (based onahipscan,WHOcriteria),andnottakinganydrugs relatedtoboneformation,includingcalciumorvitamin D supplementation, were randomly assigned to either oral800IUvitaminD 3 plus1gcalciumorplacebo,ina double-blind prospective study. We measured bio- chemical, radiographic, and bone mineral density effect parameters to evaluate the impact on the healing pro- cess. Scanning procedures of the fractured shoulder in- cluded use of a fixation device to obtain the highest possible precision. Double scans of the fractured shoulder revealed a coefficient of variation (CV) on BMD measurements that improved from 2.8% imme- diately after fracture occurrence to 1.7% at 12 weeks (P = 0.003) approaching the 1.2% levels observed over the healthy shoulder. BMD was similar in the two groups at baseline (active 0.534 g/cm 2 vs. placebo 0.518 g/cm 2 ), and both increased over the 12-week observationperiod,withpeaklevelsinweek6.Byweek 6 BMD levels were higher in the active group (0.623 g/cm 2 ) compared with the placebo group (0.570 g/cm 2 , P = 0.006). Thirty seven percent of the patients pre- sentedwithvitaminDlevelsbelow30nmol/l,indicative of mild vitamin D insufficiency. In conclusion, we have demonstrated that it is possible to quantify callus for- mation of the PHF with sufficiently high precision to demonstrate the positive influence of vitamin D 3 and calcium over the first 6 weeks after fracture. Whether this results in more stable fractures, extends to other fracture types, or applies to other osteogenic bone agentssuchasbisphosphonatesremainstobeexamined. Key words: Reduced BMD — Fracture — Healing — Vitamin D 3 — Calcium Theformationofcallusisthenaturalrepairandfixation responsetoafractureintheabsenceofartificialfixating devices including casts or osteosynthetic materials. Callusresponseisalsoanexpressionoffracturehealing [1, 2], and, by numerically measuring the amount of callus, it is possible to quantify the healing process. The conservatively treated nondisplaced proximal humerus fracture (PHF) is ideal to follow the genuine healingbycallusresponse,sinceitisnotfixatedinacast or by osteosynthetic materials [1, 2]. We have recently establishedamethodologyforthemeasurementofbone mass with high precision using BMD scanning over the unfractured shoulder region [3]. We hypothesize that BMD scanning provides a suitable methodology to quantify changes in callus formation over the PHF, enabling us to determine the impact of medical inter- vention during the healing process. Several animal studies have shown that vitamin D treatment promotes both fracture healing and mechan- icalstrengthofthecallus[4–6].However,nodataonthe role of vitamin D and calcium treatment in fracture healing are currently available in humans. The aim of this study was to follow the healing pro- cessoftheosteoporotic/osteopenicfracturebymeansof measuring changes in the calcium density (callus) over the fracture region using BMD scanning. For this pur- pose, only patients with a PHF and reduced BMD (T- score< )1)wereincludedinthestudy,inpartbecause reduced BMD is highly prevalent in subjects with this type of fracture, and in part to obtain a reasonably homogenic group of patients. The other aim of this study was to investigate the potential of an oral sup- plement of calcium and vitamin D 3 mitigating some of Correspondence to: A. M. Doetsch; E-mail: doetsch@mail.dk Calcif Tissue Int (2004) 75:183–188 DOI: 10.1007/s00223-004-0167-0