Reduced Bone Turnover Markers Research Articles

Bone density and markers of bone turnover in predicting fracture risk and how changes in these measures predict fracture risk reduction

Surrogate markers in clinical medicine provide a useful means to assess therapeutic response to pharmacologic therapy in a wide range of chronic disease states. In the area of osteoporosis, the surrogate markers of change in bone mineral density (BMD) and bone turnover markers (BTM) provide the clinician with a means of assessing the biologic response to osteoporosis-specific pharmacologic agents. Increases in BMD and/or reductions in BTM can independently be correlated to reductions in vertebral and nonvertebral fracture risk. In managing osteoporosis patients, the BTM change at an earlier point of time after initiation of therapy and a change in BTM can provide earlier feed-back to the patient and clinician regarding issues such as compliance and a bone biologic response. An increase in BMD at 12 or 24 months after initiation of therapy is also evidence of an improvement in bone strength though with antiresorptive agents no change in BMD may also be associated with risk reduction within clinical trial sets. In this regard, changes in BMD and BTM are complimentary in their application to patient management.

Role of oestrogen in the regulation of bone turnover at the menarche

The rise in oestrogen levels at menarche in girls is associated with a large reduction in bone turnover markers. This reduction reflects the closure of the epiphyseal growth plates, the reduction in periosteal apposition and endosteal resorption within cortical bone, and in bone remodelling within cortical and cancellous bone. Oestrogen promotes these changes, in part, by promoting apoptosis of chondrocytes in the growth plate and osteoclasts within cortical and cancellous bone. The period of early puberty is associated with an increased risk of fracture, particularly of the distal forearm, and this may be related to the high rate of bone turnover. A late menarche is a consistent risk factor for fracture and low bone mineral density in the postmenopausal period; models that might explain this association are considered.

The efficacy and tolerability of risedronate on bone mineral density and bone turnover markers in osteoporotic Chinese women: a randomized placebo-controlled study

Osteoporosis has become an important health problem in postmenopausal Asian populations as the prevalence of hip and vertebral fractures in some Asian countries has risen to approach that of Caucasian populations. Risedronate, a pyridinyl-bisphosphonate agent, is a potent inhibitor of bone resorption. Risedronate increases bone mineral density (BMD), reduces markers of bone turnover, and reduces the risk of fractures in Caucasian postmenopausal women. To determine the efficacy and tolerability of risedronate in Chinese, a multicenter, randomized, double blind, placebo controlled study was performed in Hong Kong. Sixty-five (65) postmenopausal osteoporotic Southern Chinese women, aged 67 ± 6 years, were randomly assigned to receive either risedronate 5 mg daily ( n = 31) or placebo ( n = 34) for 12 months. All women received calcium carbonate 500 mg daily and vitamin D 400 IU daily. Mean baseline BMD T-score at the spine and total hip was −3.4 and −2.6, respectively. A significant increase in spine BMD was already evident at month 3 of risedronate treatment ( P < 0.001). Risedronate significantly increased BMD and reduced bone turnover markers as compared with placebo. The risedronate group had significant increase in BMD at 12 months at both the spine and hip when compared with the placebo group (L1–4 6.6% vs. 0.4%, P < 0.001; total hip 2.7% vs. 0.3, P < 0.0001; femoral neck 1.8% vs. 1.1%, P < 0.02; trochanter 4% vs. 1.1%, P < 0.0001, respectively). Significant changes in urine N-telopeptide (NTx) and serum osteocalcin were evident as early as 1 and 3 months, respectively, with risedronate treatment. No significant changes were seen in both BMD and bone markers in the placebo group. Risedronate was well tolerated without major adverse effects. We conclude that risedronate is an effective and well-tolerated agent for the treatment of postmenopausal osteoporosis in Asian population.

Comparison of the effects of two different types of calcium supplementation on markers of bone metabolism in a postmenopausal osteopenic population with low calcium intake: a double-blind placebo-controlled trial

Objective To investigate calcium supplements in postmenopausal women. Calcium supplements in postmenopausal women with a low calcium intake have been shown to prevent osteoporotic vertebral fracture, but calcium is variably absorbed and often poorly tolerated, which may limit effectiveness.Methods The study compared the efficacy and tolerability of 500 mg/day of calcium in the form of ossein-hydroxyapatite (OHC) versus 500 mg/day of tricalcium phosphate (TCP) and placebo in the prevention of postmenopausal bone loss. This was a prospective randomized study enrolling 153 postmenopausal osteopenic women. Serum and urine markers of bone turnover were collected at 3 and 6 months. Bone density measurement was performed at baseline and 6 months in all participants, and at 12 months in women taking OHC.Results At 3 and 6 months, both TCP and OHC decreased serum markers of bone formation significantly, compared with placebo. At 6 months, TCP and OHC decreased osteocalcin by 9.9% and 12.3%, respectively; the aminoterminal propeptide of type I procollagen (PINP) was decreased by 5.3% and 6.3%, respectively; bone-specific alkaline phosphatase was decreased by 4.3% and 6.7%, respectively, compared with baseline. The effects on bone resorption markers or on bone mineral density did not reach statistical significance, although OHC increased bone density by 0.8% at the spine at 12 months. Both forms of calcium were well tolerated and did not differ from placebo in terms of side-effects.Conclusions While both OHC and TCP were well tolerated and significantly reduced bone turnover markers, the effect of ossein-hydroxyapatite seems slightly superior to that of tricalcium phosphate.

RETINOIC ACID SUPPRESSES INTERLEUKIN 6 PRODUCTION IN NORMAL HUMAN OSTEOBLASTS

Systemic long-term retinoid therapy for chronic skin diseases significantly reduced bone turnover markers within days and led to bone abnormalities. Retinoic acid (RA) plays a key role in the regulation of mouse bone cell proliferation, differentiation and functions. Meanwhile, there is little information of RA effect on human osteoblast and osteoclast cell development and function. Interleukin 6 (IL-6) is a pleiotropic cytokine with profound effects on bone metabolism. Thus, the present study examined the RA effect on cell differentiation, alkaline phosphatase and osteocalcin production as well as IL-6 production in normal human osteoblasts. The number of large differentiated osteoblast cells decreased in RA-treated culturesP <0.05. The production of bone specific markers, alkaline phosphatase and osteocalcin, was also reduced in RA-treated cultures. Normal human osteoblasts produced 31.0±4.8pg IL-6 per ml in control cultures. Within 24h, RA at all four concentrations reduced Il-6 production from normal human osteoblasts. The pharmacological concentration of 10−5M RA suppressed 90% of IL-6 production. The present study shows for the first time that RA profoundly inhibits IL-6 production in normal human osteoblasts within 24h and in a dose-dependent manner. RA was shown previously to inhibit IL-6 production in several other normal and malignant human cell types. The associated decrease in osteoblast cell differentiation, alkaline phosphatase and osteocalcin production could result from the rapid RA-inhibition of IL-6 production. Thus, RA inhibition of IL-6 production in normal human osteoblasts may contribute to the bone abnormalities seen after systemic long-term retinoid therapy in some patients.