9 10 BRITISH MEDICAL JOURNAL VOLUME 281 4 OCTOBER 1980 (95-6 mg/100 ml)) a n d creatinine (170 1tmol/l ( 1 9 mg/100 ml)) concentrations, b u t electrolyte, liver function, a nd haematological values were normal. An excretory pyclogram performed i n Ma y 1980 showed no abnormalities. T wo mid-stream specimens o f (MSU) showed gross pyuria ( u p to 3 0 x 109/1 white blood cells) b ut n o significant bacterial growth aerobically. T h e result o f culture f o r Mycobacterium tuberculosis w a s negative. Subsequent MSUs were cultured both anaerobically a n d aerobically using a dilution technique,3 a n d t h e findings ar e shown in t h e table. A microaerophilic species, Streptococcus milleri (107/ml), and four species o f strict anaerobes were present in t w o successive specimens, with gross pyuria, b t f e w aerobic organisms were isolated ( < 103/ml). Days 0 2 0 4 0 6 0 8 0 1 0 0 1 2 0 14 0 160 180 2 0 0 22 0 2 4 0 26 0 2 8 0 S t r mierm + +_ + _ + + _ - a ' StrictO7nmny . anaerobic 4 4 ptococc 3 bactero'ides * 0 growth s p - - SPePtoacSPP~ spplO9/ml Aerobic growth . - Ni t rofurantoin Treatment - -' Cephradine Amoxycillin Patient away Amoxycillin Sulphadiazine 10 0 1 0 . WBCx1O9/t 1. 0 T 1 i 0 . 2 t t i Serial results o f MSU culture a n d white cell counts a n d treatment given. Three separate courses o f antibiotic treatment, first with cephradine ( 1 g 12-hourly) then twice with amoxycillin (500 mg 8-hourly), a l l produced a similar clinical response: the bacteriuria w a s initially eradicated a n d pyuria greatly reduced, b u t relapse occurred each time, S t r milleri returning in large numbers (>107/ml). Peptococcus sp w a s also present (101/ml) o n o n e occasion. Bacteriological relapse w a s associated with a n increase i n white cell excretion. Eventually Str milleri disappeared spontaneously, b ut an aerobic streptococcus (106/ml) wa s then found. Combined treatment with nitro- furantoin ( 5 0 m g 12-hourly) a n d sulphadiazine (150 m g 12-hourly) cleared t h e streptococci, b u t the urine then contained large numbers o f anaerobic species (predominantly Bacteroides spp, 109/ml). T h e patient remained symptom-free a t a l l times. I n view o f t he recurrent nature o f relapses a n d reinfections, a n d t h e fact that t h e patient w a s well, no further antibiotic treatment w a s given, a n d t h e infection cleared spontaneously. Four months later S t r milleri (106/ml) wa s again found;phenoxymethylpenicillin (250 mg 8-hourly)cleared this infection, a n d since March 1980 t he urine h as remained free of anaerobes an d microaerophilic bacteria. Comment Anaerobes a n d microaerophilic bacteria ma y b e isolated i n large numbers ( : 105/ml) i n mid-stream urine specimens from patients without signs o f infection' and from normal subjects (unpublished work). Nevertheless, we a r e convinced, after repeated cultures a nd temporary eradication o f bacteriuria together with concomitant reductions of pyuria after treatment, that genuine infective processes were occurring i n this patient. Ou r findings lend weight t o t h e theory that growth conditions f o r strict anaerobes a n d microaerophilic organisms ar e favourable i n t h e urinary tract4 a n d that such species c a n cause true infections. I n this case S t r milleri w a s usually t h e predominant species, often accompanied by several species strict anaerobes in large numbers ( -10)/ml) always including B melaninogenicus. Metronidazole was n o t given because i t i s inactive against S t r milleri. Ou r findings highlight t h e difficulty o f treating infections o f this nature, which c a n b e associated with- urological abnormalities. Thus when persistent "sterile pyuria" i s reported t h e clinician should look fo r microaerophilic a n d anaerobic bacteria a s well a s excluding infection b y M tuberculosis. I n this patient t h e use of appropriate culture techniques enabled us t o diagnose th e microaerophilic a n d anaerobic infection a n d eventually t o eradicate i t. Maskell , Pead L , Allen J . T h e puzzle of "urethral syndrome": a possible answer? Lancet 1979;i:1058-9. 2 Meijer-Severs G J , Aarnoudse J G , Mensink WFA, Dankert K . T h e presence o f antibody-coated anaerobic bacteria i n asymptomatic bacteriuria during pregnancy. J Infect D i s 1979;140:653-8. 3 Gargan R A, Brumfitt W , Hamilton-Miller JMT. Do anaerobes cause urinary infection ? Lancet 1980;i:37. 4 Dankert J , Mensink WFA, Aarnoudse J G , Meijer-Severs GJ, Huisjes H J . T h e prevalence o f anaerobic bacteria i n suprapubic bladder aspirates obtained from pregnant women. Zentralbl Bakteriol (Orig A ) 1979;244: 260-7. 5 Finegold S M, Miller LG , Merrill S L, Posnick DJ. Significance o f anaerobic a n d capnophilic bacteria isolated from t h e urinary tract. I n : Kass EH , e d . Progress i n pyelonephritis. Philadelphia: F A Davis, 1965: 159-78. (Accepted 22 July 1980) Urinary Infection Clinic and Department o f Medical Microbiology, Royal Free Hospital, London NW3 W BRUMFITT, M D , FRCP, professor o f medical microbiology R A GARGAN, FIMLS, senior research assistant J M T HAMILTON-MILLER, MRCPATH, senior lecturer in medical micro- biology Osteomalacia developing during treatment o f osteoporosis with sodium fluoride an d vitamin D Combined treatment with sodium fluoride, calcium, an d vitamin D i s claimed t o b e beneficial in some patients with osteoporosis.' 2 Fluoride alone leads t o accumulation o f unmineralised bone, producing t h e histological picture o f osteomalacia. Th e addition o f calcium o r vitamin D, o r both, i s believed t o prevent this complication.' 2 We report a case where osteomalacia developed during sodium fluoride treatment despite large doses of vitamin D a n d associated high plasma 25-hydroxyvitamin D (25-OHD) concentrations. Case report A 61-year-old woman presented i n 1978 with a 15-year history o f lower back pain which h a d rapidly increased over t he previous nine months. Plasma concentrations were: calcium 2-50 mmol/l ( 1 0 mg/100 ml), phosphate 1 - 1 mmol/l ( 3 4 mg/l00 ml), a n d plasma alkaline phosphatase 9 KA U/100 ml . Radiographs showed severe osteoporosis with vertebral compression fractures o f T 7 , 8 , a n d 11 nd L 1 , 3 , a n d 5 . Iliac bone tissue w a s normal on biopsy (table). Sodium fluoride 50 mg daily, vitamin D, 5 0 0 0 0 U weekly, Quantitative bone histology before a n d after sodium fluoride an d vitamin D treatment. h e mineralisation rate was n o t measured i n t h e first biopsy Before After treatment treatment Normal (May (Mar ch (me an ± S D) 1978) 1980) Cancellous bone volume ( ° total cancellous area) 2 1 5 25 6 237 ±4 9 Osteoid volume ( total cancellous volume) 3 9 1 8 5 3 9±19 Total resorption surface ( U O total cancellous surface). 7 3 77 7 30±12 Calcification fronts ( " total osteoid surface) 60-0 33-3 76 4 ±7-8 Mineralisation rate (,uday) <0-1 0-64±0-06 a nd calcium gluconate 6 0 0 mg twice daily were given b y mouth. Calcium supplements were discontinued after tw o months because t h e patient wa s unable t o tolerate them. Dietary calcium intake was assessed at 8 5 1 mg/day. Renal function was normal. T he plasma 25-OHD concentration was measured by competitive protein-binding assay4 an d plasma 1,25-dihydroxyvitamin D3 (l,25-(OH)2D3) b y radioimmunoassay.5 Undecalcified sections (8 tm) o f transiliac bone tissue were quantitatively assessed. Control v al ue s were obtained from s i x healthy women aged 51-69 years (mean 58). T h e mineral- isation rate was measured b y double labelling with demethylchlortetra- cycline. During treatment bone pain increased a n d three further vertebral com- pression fractures occurred. Plasma calcium, phosphate, a n d alkaline phosphatase concentrations remained normal throughout treatment an d in March 1980 were 2 4 9 mmol/l ( 1 0 mg/100 ml), 0 9 mmol/l (2-86 mg/l00 ml), a n d 1 1 KA U/100 ml respectively. A t this time t h e plasma 25-OHD concen- tration was 1 2 5 nmol/l ( 50 ng/ml) a n d t h e plasma 1,25-(OH)2D3 was 1 9 pg/ml. Bone biopsy i n March 1980 showed moderately severe osteomalacia an d secondary hyperparathyroidism. Most o f t he boneand osteoid showed a normal lamellar pattern under polarised light.