Osteoporosis is a common chronic disease and therefore a long-term management plan based on disease severity, comorbidities, other pharmacological treatments, gender, age and patient preferences is necessary. Consideration of treatment breaks may be included in the long-term management plan if the patient has been treated with a bisphosphonate, the disease is less severe, the response to treatment has been satisfactory and the risk of future fracture is estimated to be low. This perspective reviews the current evidence for long-term treatment with bisphosphonates and off treatment effects. Approaches to decision making and monitoring of treatment breaks are discussed.
Katrine Hygum, Jakob Starup-Linde, Torben Harsløf, Peter Vestergaard and Bente L Langdahl
To investigate the differences in bone turnover between diabetic patients and controls.
A systematic review and meta-analysis.
A literature search was conducted using the databases Medline at PubMed and EMBASE. The free text search terms ‘diabetes mellitus’ and ‘bone turnover’, ‘sclerostin’, ‘RANKL’, ‘osteoprotegerin’, ‘tartrate-resistant acid’ and ‘TRAP’ were used. Studies were eligible if they investigated bone turnover markers in patients with diabetes compared with controls. Data were extracted by two reviewers.
A total of 2881 papers were identified of which 66 studies were included. Serum levels of the bone resorption marker C-terminal cross-linked telopeptide (−0.10 ng/mL (−0.12, −0.08)) and the bone formation markers osteocalcin (−2.51 ng/mL (−3.01, −2.01)) and procollagen type 1 amino terminal propeptide (−10.80 ng/mL (−12.83, −8.77)) were all lower in patients with diabetes compared with controls. Furthermore, s-tartrate-resistant acid phosphatase was decreased in patients with type 2 diabetes (−0.31 U/L (−0.56, −0.05)) compared with controls. S-sclerostin was significantly higher in patients with type 2 diabetes (14.92 pmol/L (3.12, 26.72)) and patients with type 1 diabetes (3.24 pmol/L (1.52, 4.96)) compared with controls. Also, s-osteoprotegerin was increased among patients with diabetes compared with controls (2.67 pmol/L (0.21, 5.14)).
Markers of both bone formation and bone resorption are decreased in patients with diabetes. This suggests that diabetes mellitus is a state of low bone turnover, which in turn may lead to more fragile bone. Altered levels of sclerostin and osteoprotegerin may be responsible for this.
Bente L Langdahl, Anne Gitte R Loft, Erik F Eriksen, Leif Mosekilde and Peder Charles
Langdahl BL, Loft AGR, Eriksen EF, Mosekilde L, Charles P. Bone mass, bone turnover and body composition in former hypothyroid patients receiving replacement therapy. Eur J Endocrinol 1996;134:702–9. ISSN 0804–4643
The aim of the present cross-sectional study was to disclose whether long-term thyroxine replacement therapy (TRT) in primary hypothyroidism causes osteopenia. We compared 36 adult biochemically and clinically euthyroid patients who had received TRT for more than 5 years (mean 13 years) for primary hypothyroidism with 80 sex- and age-matched normal controls. Height, body weight and lean body mass were similar, but the patients had 21% higher fat body mass (p < 0.01) than their controls. Furthermore, compared to controls the patients had 29% higher serum thyroxine (T4) and 31% higher serum free T4 index (FT4I) levels (p < 0.001), whereas serum triiodothyronine (T3) and FT3I levels were both reduced by 7% (p < 0.05). In the patients, serum TSH was reduced significantly (p < 0.001). No significant differences were observed between patients and normals in regional or total bone mineral content or bone mineral density levels, apart from 20% higher lumbar bone mineral content among the premenopausal patients (p < 0.05). Surprisingly, the mean serum calcium level was slightly elevated (2.38 ± 0.08 vs 2.33 ± 0.07 nmol/l, p < 0.001), serum phosphate decreased (1.13 ± 0.19 vs 1.23 ± 0.16 mmol/l, p < 0.01) and 24-h renal calcium excretion was reduced by 19% (p < 0.05). No changes were observed in serum magnesium, intact parathyroid hormone or calcitriol. The biochemical markers of bone resorption (serum carboxyterminal telopeptide of type I collagen, renal excretion of hydroxyproline, pyridinoline and deoxypyridinoline) and formation (serum levels of carboxyterminal propeptide of type I procollagen, osteocalcin and total and bone alkaline phosphatase) were similar in the two groups. We conclude that long-term thyroxine replacement therapy in primary hypothyroidism does not exert a negative effect on bone mass or alter bone turnover.
Bente L Langdahl, University Department of Endocrinology and Metabolism, Aarhus Amtssygehus, Tage Hansensgade 2, DK-8000, Aarhus C, Denmark