Table 2

Interventional studies to prevent and treat osteoporosis in patients with liver disease

SourceInterventionDurationType of studySubjectsSize (n)Outcome
C, control group; T, treatment group; FN, femoral neck; LS, lumbar spine; PBC, primary biliary cirrhosis; im, intramuscularly; sc, subcutaneously.
Wolfhagen et al37T=cyclical etidronate 400 mg and calcium 500 mg/day; C=calcium 500 mg/day. All on prednisolone1 yRandomised placebo controlledPBC stage III/IV; Childs Pugh A12; C=6, T=6BMD (L2–4): T=+0.4% (p=0.001), C=−3%; BMD (FN): no change, no change in incident fractures. Cyclical etidronate prevents bone loss associated with steroid treatment in PBC
Guanabens et al38T1=cyclical etidronate 400 mg; T2=sodium fluoride 50 mg/day. All received calcium 1–1.5 g/day in addition to diet and vitamin D 226 μg every 2 weeks orally2 yRandomisedPBC (all F); age 57 (1.3) y; 19% previous fracture32; T1=16, T2=16BMD: T1=+0.53% LS, no change FN; T2=no change in LS; 5.89% at FN. Vertebral fracture: T1=0/16, T2=2/16. Cyclical etidronate more effective in preventing bone loss in PBC than sodium fluoride
Pares et al39T1=alendronate 10 mg/day; T2=cyclical etidronate 400 mg. All received calcium 1–1.5 g and vitamin D 266 μg orally1 yRandomised26; T1=13, T2=13BMD (L2–4): T1=+4.8% (p=0.001), T2=+0.587 (NS); BMD (FN): T1=+3.44% (p=0.01), T2=+1.69% (NS). Veretebral fracture nil. Non-vertebral fracture: T1=2/12, T2=1/13. Alendronate increases bone mass in PBC and has greater effect than etidronate
Vitamin D
Matloff et al40T1=25-hydroxy vitamin D 20–120 μg/day. All calcium to 1 g/day1 yNon-controlled open, non-randomisedPBC (all female). All bone disease10Bone mineral content (photon absorpt) decreased in 8/8 patients. 25-hydroxyvitamin D ineffective in reversing bone loss in PBC
Herlong et al41T1=25-hydroxyvitamin D 100 μg/day1 yNot controlled open, non-randomisedPBC (all F). Low vitamin D in 11/15 corrected by treatment. Age 48 (33–66 y). Postmenopause 5/1515Bone density (photon beam radius): decrease (0.82 g/cm v 0.77 g/cm; p=0.029). Despite correction of vitamin D deficiency, progression of osteoporosis seen in PBC
Eastell et al16All calcium 1.3 g/day and vitamin D2 1.25 mg/week if 25 hydroxyvitamin D low2 y median (0.5–6 y)LongitudinalPBC (all F); 38% postmenopausal. Controls aged matched normal women. BMD 7% lower in PBC than controls105BMD lumbar spine (dual photon absorptiometry): bone loss 2%/y v 1%/y in controls. Progressive bone loss despite calcium and vitamin D but no PBC controls
Crippin et al42T1=oestrogens, T2=calciumUp to 8 yRetrospective analysisPBC (stage 1–1V); 50.3 (10.2) y; 59% postmenopause; 37% BMD <fracture threshold203; T1=16, T2=187BMD (dual photon absorption): T1=+0.014 (n=16) v −0.03 (n=91) with no oestrogens; T2=no difference in 8 y FU in those receiving calcium (47% patients) or not. 16.1% (9/56) vitamin D deficient given vitamin D. 8/9 no change or fall in BMD over 1 y. Oestrogen replacement in postmenopausal women with PBC improves spine BMD. Calcium and vitamin D, even if deficient, do not improve BMD
Olsson et al43T1=oestrogen/progesterone, C=nil2 yNon-randomised controlledPBC (all F); 9/10 osteoporosis; 1/10 osteopenia10Increase BMD in HRT group.
Epstein et al44T1=calcium gluconate 40 mmol, T2=hydroxyapatite 8 g, C= nil. All received vitamin D 100 000 IU monthly im14 monthsRandomised controlledPBC (all F); postmenopausal53; T1=17, T2=15, C= 21Metacarpal cortical thickness: T1=+1.5%, T2=+6.1%, C=−5.5%. Calcium prevented bone thinning, hydroxyapatite increased cortical bone thickenening
Camisasca et al17T1=calcitonin 40 IU alt days sc for 6 months, C=calcitonin 1 IU ×2 weekly alternate months. All received vitamin D 10 000 IU im monthly. Calcium 1 g started after 6/12 drug free observation period21 monthsRandomised controlled crossover studyPBC (all F); severe osteopenia; BMD <2 SD below age matched. Excluded patients vertebral fractures. Mean age 65 y; 60% cirrhotic; 76% postmenopausal25BMD (dual photon absorption), observation period 6/12, BMD −3.5%: T=+4.3%; C +4.9%; crossover after 3/12 washout, T=−2.7%, C=−4.9%. No vertebral fractures seen. No difference in BMD between control and calcitonin but calcium had transient benefit
Floreani et al19T1=1,25 OH vitamin D 0.5 μg twice daily for 5/7 and calcium 1.5 g 1/12 and calcitonin 40 IU ×3 weekly repeated every 3 months, C=nil3 yNon-randomised controlledPBC (all F) stratified by BMD. T1=<0.800 g/cm, T2=>0.800 g/cm59; T1=23, C=36BMD (dual photon absorption): increase in T1 in follow up (p<0.05). After 11/12, 11 patients in C group BMD <0.800 g/cm and treated group. Calcitonin, vitamin D, and calcium associated with increase in BMD in PBC with low bone density
Shiomi et al45T1=1 alpha 25 OH vitamin D3 0.5 μg bd, C=nil12–57 monthsRandomised controlledCirrhosis, mean age 62 y76; T1=38, C=38BMD L2–4 (DEXA): males: T1=+1.1%, C=−0.4% mean/y; females: T1=−0.5%, C=−2.3%. Median values significant only: males: T=+0.6%, C=−1.4% (p=0.013); females: T=−0.5%, C=−1.5% (p=0.011). Calcitriol can prevent bone loss in cirrhosis